Anticipating the species jump: surveillance for emerging viral threats.

Zoonotic disease surveillance is typically triggered after animal pathogens have already infected humans. Are there ways to identify high-risk viruses before they emerge in humans? If so, then how and where can identifications be made and by what methods? These were the fundamental questions driving a workshop to examine the future of predictive surveillance for viruses that might jump from animals to infect humans. Virologists, ecologists and computational biologists from academia, federal government and non-governmental organizations discussed opportunities as well as obstacles to the prediction of species jumps using genetic and ecological data from viruses and their hosts, vectors and reservoirs. This workshop marked an important first step towards envisioning both scientific and organizational frameworks for this future capability. Canine parvoviruses as well as seasonal H3N2 and pandemic H1N1 influenza viruses are discussed as exemplars that suggest what to look for in anticipating species jumps. To answer the question of where to look, prospects for discovering emerging viruses among wildlife, bats, rodents, arthropod vectors and occupationally exposed humans are discussed. Finally, opportunities and obstacles are identified and accompanied by suggestions for how to look for species jumps. Taken together, these findings constitute the beginnings of a conceptual framework for achieving a virus surveillance capability that could predict future species jumps

Radiating Shear-Free Gravitational Collapse with Charge

We present a new shear free model for the gravitational collapse of a spherically symmetric charged body. We propose a dissipative contraction with radiation emitted outwards. The Einstein field equations, using the junction conditions and an ansatz, are integrated numerically. A check of the energy conditions is also performed. We obtain that the charge delays the black hole formation and it can even halt the collapse.Comment: 22 pages, 9 figures. It has been corrected several typos and included several references. Accepted for publication in GR

The role of Comprehension in Requirements and Implications for Use Case Descriptions

Within requirements engineering it is generally accepted that in writing specifications (or indeed any requirements phase document), one attempts to produce an artefact which will be simple to comprehend for the user. That is, whether the document is intended for customers to validate requirements, or engineers to understand what the design must deliver, comprehension is an important goal for the author. Indeed, advice on producing ‘readable’ or ‘understandable’ documents is often included in courses on requirements engineering. However, few researchers, particularly within the software engineering domain, have attempted either to define or to understand the nature of comprehension and it’s implications for guidance on the production of quality requirements. Therefore, this paper examines thoroughly the nature of textual comprehension, drawing heavily from research in discourse process, and suggests some implications for requirements (and other) software documentation. In essence, we find that the guidance on writing requirements, often prevalent within software engineering, may be based upon assumptions which are an oversimplification of the nature of comprehension. Hence, the paper examines guidelines which have been proposed, in this case for use case descriptions, and the extent to which they agree with discourse process theory; before suggesting refinements to the guidelines which attempt to utilise lessons learned from our richer understanding of the underlying discourse process theory. For example, we suggest subtly different sets of writing guidelines for the different tasks of requirements, specification and design

Potential geographic distribution of Hantavirus reservoirs in Brazil

Hantavirus cardiopulmonary syndrome is an emerging zoonosis in Brazil. Human infections occur via inhalation of aerosolized viral particles from excreta of infected wild rodents. Necromys lasiurus and Oligoryzomys nigripes appear to be the main reservoirs of hantavirus in the Atlantic Forest and Cerrado biomes. We estimated and compared ecological niches of the two rodent species, and analyzed environmental factors influencing their occurrence, to understand the geography of hantavirus transmission. N. lasiurus showed a wide potential distribution in Brazil, in the Cerrado, Caatinga, and Atlantic Forest biomes. Highest climate suitability for O. nigripes was observed along the Brazilian Atlantic coast. Maximum temperature in the warmest months and annual precipitation were the variables that most influence the distributions of N. lasiurus and O. nigripes, respectively. Models based on occurrences of infected rodents estimated a broader area of risk for hantavirus transmission in southeastern and southern Brazil, coinciding with the distribution of human cases of hantavirus cardiopulmonary syndrome. We found no demonstrable environmental differences among occurrence sites for the rodents and for human cases of hantavirus. However, areas of northern and northeastern Brazil are also apparently suitable for the two species, without broad coincidence with human cases. Modeling of niches and distributions of rodent reservoirs indicates potential for transmission of hantavirus across virtually all of Brazil outside the Amazon Basin

Study of avidity of antigen-specific antibody as a means of understanding development of long-term immunological memory after Vibrio cholerae O1 infection

The avidity of antibodies to specific antigens and the relationship of avidity to memory B cell responses to these antigens have not been studied in patients with cholera or those receiving oral cholera vaccines. We measured the avidity of antibodies to cholera toxin B subunit (CTB) and Vibrio cholerae O1 lipopolysaccharide (LPS) in Bangladeshi adult cholera patients (n = 30), as well as vaccinees (n = 30) after administration of two doses of a killed oral cholera vaccine. We assessed antibody and memory B cell responses at the acute stage in patients or prior to vaccination in vaccinees and then in follow-up over a year. Both patients and vaccinees mounted CTB-specific IgG and IgA antibodies of high avidity. Patients showed longer persistence of these antibodies than vaccinees, with persistence lasting in patients up to day 270 to 360. The avidity of LPS-specific IgG and IgA antibodies in patients remained elevated up to 180 days of follow-up. Vaccinees mounted highly avid LPS-specific antibodies at day 17 (3 days after the second dose of vaccine), but the avidity waned rapidly to baseline by 30 days. We examined the correlation between antigen-specific memory B cell responses and avidity indices for both antigens. We found that numbers of CTB- and LPS-specific memory B cells significantly correlated with the avidity indices of the corresponding antibodies (P < 0.05; Spearman's ρ = 0.28 to 0.45). These findings suggest that antibody avidity after infection and immunization is a good correlate of the development and maintenance of memory B cell responses to Vibrio cholerae O1 antigens

An Anatomy Massive Open Online Course as a Continuing Professional Development Tool for Healthcare Professionals

Massive open online courses (MOOCs) remain a novel and under-evaluated learning tool within anatomical and medical education. This study aimed to provide valuable information by using an anatomy MOOC to investigate the demographic profile, patterns of engagement and self-perceived benefits to healthcare professionals. A 21-item survey aimed at healthcare professionals was embedded into the Exploring Anatomy: The Human Abdomen MOOC, in April 2016. The course attracted 2711 individual learners with 94 of these completing the survey, and 79 of those confirming they worked full- or part-time as healthcare professionals. Variations in use across healthcare profession (allied healthcare professional, nurse or doctor) were explored using a Fisher’s exact test to calculate significance across demographic, motivation and engagement items; one-way ANOVA was used to compare self-perceived benefits. Survey data revealed that 53.2% were allied healthcare professionals, 35.4% nurses and 11.4% doctors. Across all professions, the main motivation for enrolling was to learn new things in relation to their clinical practice, with a majority following the prescribed course pathway and utilising core, and clinically relevant, material. The main benefits were in relation to improving anatomy knowledge, which enabled better support for patients. This exploratory study assessing engagement and self-perceived benefits of an anatomy MOOC has shown a high level of ordered involvement, with some indicators suggesting possible benefits to patients by enhancing the subject knowledge of those enrolled. It is suggested that this type of learning tool should be further explored as an approach to continuing professional, and interprofessional, education

An experimental study of executive function and social impairment in Cornelia de Lange syndrome

Background Extreme shyness and social anxiety is reported to be characteristic of adolescents and adults with Cornelia de Lange syndrome (CdLS); however, the nature of these characteristics is not well documented. In this study, we develop and apply an experimental assessment of social anxiety in a group of adolescents and adults with CdLS to determine the nature of the social difficulties and whether they are related to impairments in executive functioning. Methods A familiar and unfamiliar examiner separately engaged in socially demanding tasks comprising three experimental conditions with a group of individuals with CdLS (n = 25; % male = 44; mean age = 22.16; SD = 8.81) and a comparable group of individuals with Down syndrome (DS; n = 20; % male = 35; mean age = 24.35; SD = 5.97). Behaviours indicative of social anxiety were coded. The Behavior Rating Inventory of Executive Function-Preschool version, an informant measure of executive function, was completed by participants’ caregivers. Results Significantly less verbalisation was observed in the CdLS group than the DS group in conditions requiring the initiation of speech. In the CdLS group, impairments in verbalisation were not associated with a greater degree of intellectual disability but were significantly correlated with impairments in both planning and working memory. This association was not evident in the DS group. Conclusions Adolescents and adults with CdLS have a specific difficulty with the initiation of speech when social demands are placed upon them. This impairment in verbalisation may be underpinned by specific cognitive deficits, although further research is needed to investigate this fully

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

Varieties of living things: Life at the intersection of lineage and metabolism

publication-status: Publishedtypes: Articl

Heparan sulfate proteoglycans: structure, protein interactions and cell signaling

Heparan sulfate proteoglycans are ubiquitously found at the cell surface and extracellular matrix in all the animal species. This review will focus on the structural characteristics of the heparan sulfate proteoglycans related to protein interactions leading to cell signaling. The heparan sulfate chains due to their vast structural diversity are able to bind and interact with a wide variety of proteins, such as growth factors, chemokines, morphogens, extracellular matrix components, enzymes, among others. There is a specificity directing the interactions of heparan sulfates and target proteins, regarding both the fine structure of the polysaccharide chain as well precise protein motifs. Heparan sulfates play a role in cellular signaling either as receptor or co-receptor for different ligands, and the activation of downstream pathways is related to phosphorylation of different cytosolic proteins either directly or involving cytoskeleton interactions leading to gene regulation. The role of the heparan sulfate proteoglycans in cellular signaling and endocytic uptake pathways is also discussed.Proteoglicanos de heparam sulfato são encontrados tanto superfície celular quanto na matriz extracelular em todas as espécies animais. Esta revisão tem enfoque nas características estruturais dos proteoglicanos de heparam sulfato e nas interações destes proteoglicanos com proteínas que levam à sinalização celular. As cadeias de heparam sulfato, devido a sua variedade estrutural, são capazes de se ligar e interagir com ampla gama de proteínas, como fatores de crescimento, quimiocinas, morfógenos, componentes da matriz extracelular, enzimas, entreoutros. Existe uma especificidade estrutural que direciona as interações dos heparam sulfatos e proteínas alvo. Esta especificidade está relacionada com a estrutura da cadeia do polissacarídeo e os motivos conservados da cadeia polipeptídica das proteínas envolvidas nesta interação. Os heparam sulfatos possuem papel na sinalização celular como receptores ou coreceptores para diferentes ligantes. Esta ligação dispara vias de sinalização celular levam à fosforilação de diversas proteínas citosólicas ou com ou sem interações diretas com o citoesqueleto, culminando na regulação gênica. O papel dos proteoglicanos de heparam sulfato na sinalização celular e vias de captação endocítica também são discutidas nesta revisão.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo (UNIFESP) Departamento de BioquímicaUniversidade Federal de São Paulo (UNIFESP) Departamento de OftalmologiaUNIFESP, Depto. de BioquímicaUNIFESP, Depto. de OftalmologiaSciEL