Molecular pathogenesis of H5 highly pathogenic avian influenza: the role of the haemagglutinin cleavage site motif

The emergence of H5N1 highly pathogenic avian influenza has caused a heavy socio-economic burden through culling of poultry to minimise human and livestock infection. Although human infections with H5N1 have to date been limited, concerns for the pandemic potential of this zoonotic virus have been greatly intensified following experimental evidence of aerosol transmission of H5N1 viruses in a mammalian infection model. In this review, we discuss the dominance of the haemagglutinin cleavage site motif as a pathogenicity determinant, the host-pathogen molecular interactions driving cleavage activation, reverse genetics manipulations and identification of residues key to haemagglutinin cleavage site functionality and the mechanisms of cell and tissue damage during H5N1 infection. We specifically focus on the disease in chickens, as it is in this species that high pathogenicity frequently evolves and from which transmission to the human population occurs. With >75% of emerging infectious diseases being of zoonotic origin, it is necessary to understand pathogenesis in the primary host to explain spillover events into the human population.

A new rodent model to assess blood stage immunity to the plasmodium falciparum antigen merozoite surface protein 119 reveals a protective role for invasion inhibitory antibodies

Antibodies capable of inhibiting the invasion of Plasmodium merozoites into erythrocytes are present in individuals that are clinically immune to the malaria parasite. Those targeting the 19-kD COOH-terminal domain of the major merozoite surface protein (MSP)-119 are a major component of this inhibitory activity. However, it has been difficult to assess the overall relevance of such antibodies to antiparasite immunity. Here we use an allelic replacement approach to generate a rodent malaria parasite (Plasmodium berghei) that expresses a human malaria (Plasmodium falciparum) form of MSP-119. We show that mice made semi-immune to this parasite line generate high levels of merozoite inhibitory antibodies that are specific for P. falciparum MSP-119. Importantly, protection from homologous blood stage challenge in these mice correlated with levels of P. falciparum MSP-119–specific inhibitory antibodies, but not with titres of total MSP-119–specific immunoglobulins. We conclude that merozoite inhibitory antibodies generated in response to infection can play a significant role in suppressing parasitemia in vivo. This study provides a strong impetus for the development of blood stage vaccines designed to generate invasion inhibitory antibodies and offers a new animal model to trial P. falciparum MSP-119 vaccines.

Unique IL-13Rα2-based HIV-1 vaccine strategy to enhance mucosal immunity, CD8(+) T-cell avidity and protective immunity.

We have established that mucosal immunization can generate high-avidity human immunodeficiency virus (HIV)- specific CD8þ T cells compared with systemic immunization, and interleukin (IL)-13 is detrimental to the functional avidity of these T cells. We have now constructed two unique recombinant HIV-1 vaccines that co-express soluble or membrane-bound forms of the IL-13 receptor a2 (IL-13Ra2), which can ‘‘transiently’’ block IL-13 activity at the vaccination site causing wild-type animals to behave similar to an IL-13 KO animal. Following intranasal/intramuscular prime-boost immunization, these IL-13Ra2-adjuvanted vaccines have shown to induce (i) enhanced HIV-specific CD8þ Tcells with higher functional avidity, with broader cytokine/chemokine profiles and greater protective immunity using a surrogate mucosal HIV-1 challenge, and also (ii) excellent multifunctional mucosal CD8þ T-cell responses, in the lung, genito-rectal nodes (GN), and Peyer’s patch (PP). Data revealed that intranasal delivery of these IL-13Ra2-adjuvanted HIV vaccines recruited large numbers of unique antigen-presenting cell subsets to the lung mucosae, ultimately promoting the induction of high-avidity CD8þ Tcells. We believe our novel IL-13R cytokine trap vaccine strategy offers great promise for not only HIV-1, but also as a platform technology against range of chronic infections that require strong sustained high-avidity mucosal/systemic immunity for protection.

Losing innocence : finding the line between emotional bonds and boundaries in protective service work

This paper builds on existing literature on the notion of emotional labour by investigating work in a child protective service environment. Notable characteristics of formal organisations, such as child protective services, are that they operate within a legal framework and that workers' professional duties have great influence on clients. This paper examines the intricacies of the worker-client relationship and the emotional dynamics of the service interactions by interviewing a group of workers in a public hospital in Victoria, Australia. This research extricates the complexities in the client-worker relationship by examining a range of work characteristics including their roles as professional caregivers, the emotional bonds and boundaries in the workers-client relationship, the intensity and magnitude of felt and displayed emotions, as well as the self-management of emotions and clients' emotions. This study adds to existing knowledge on the emotional expressions, experiences and regulation of emotions of the professional work lives in a child protective service work environment.
This paper is divided into the following sections. The first section details protective service work within the larger framework of human service work, and how the worker-client interface is different from other front-line service work. This is followed the need to examine the emotional dynamics of work in a child protective service organisation. Next, a study of these emotional dynamics in a child protective service organisation is reported. The paper concludes with a consideration of the wider implications for the sociology of protective service work, and how affective issues differ other service work roles.

Tanshinone IIB, a primary active constituent from Salvia miltiorrhza, exhibits neuro-protective activity in experimentally stroked rats

Tanshinone IIB (TSB) is a major active constituent of the root of Salvia miltiorrhiza (Danshen) used in the treatment of acute stroke. Danshen extracts and TSB have shown marked neuron-protective effects in mouse studies but there is a lack of clinical evidence for the neuron-protective effects of Danshen and its active ingredients. This study investigated the neuron-protective effects of TSB in experimentally stroked rats. TSB at 5 and 25 mg/kg by intraperitoneal injection significantly reduced the focal infarct volume, cerebral histological damage and apoptosis in rats subjected to middle cerebral artery occlusion (MCAO) compared to MCAO rats receiving vehicle. This study demonstrated that TSB was effective in reducing stroke-induced brain damage and may represent a novel drug candidate for further development. Further mechanistic studies are needed for the neuron-protective activity of TSB.

Evidence for a common role for the serine-type Plasmodium falciparum serine repeat antigen proteases : implications for vaccine and drug design

Serine repeat antigens (SERAs) are a family of secreted “cysteine-like” proteases of Plasmodium parasites. Several SERAs possess an atypical active-site serine residue in place of the canonical cysteine. The human malaria parasite Plasmodium falciparum possesses six “serine-type” (SERA1 to SERA5 and SERA9) and three “cysteine-type” (SERA6 to SERA8) SERAs. Here, we investigate the importance of the serine-type SERAs to blood-stage parasite development and examine the extent of functional redundancy among this group. We attempted to knock out the four P. falciparum serine-type SERA genes that have not been disrupted previously. SERA1, SERA4, and SERA9 knockout lines were generated, while only SERA5, the most strongly expressed member of the SERA family, remained refractory to genetic deletion. Interestingly, we discovered that while SERA4-null parasites completed the blood-stage cycle normally, they exhibited a twofold increase in the level of SERA5 mRNA. The inability to disrupt SERA5 and the apparent compensatory increase in SERA5 expression in response to the deletion of SERA4 provides evidence for an important blood-stage function for the serine-type SERAs and supports the notion of functional redundancy among this group. Such redundancy is consistent with our phylogenetic analysis, which reveals a monophyletic grouping of the serine-type SERAs across the genus Plasmodium and a predominance of postspeciation expansion. While SERA5 is to some extent further validated as a target for vaccine and drug development, our data suggest that the expression level of other serine-type SERAs is the only barrier to escape from anti-SERA5-specific interventions.

Individual, family, school, and community risk and protective factors for depressive symptoms in adolescents : a comparison of risk profiles for substance use and depressive symptoms

This study examines the relationship between adolescent depressive symptoms and risk and protective factors identified for substance use. A questionnaire, developed to measure these factors in a young persons community, family, school, peer group, and individual characteristics for substance use, was used to assess associations with self-reported depressive symptoms. Data were provided by a representative sample of 8984 secondary school students in Victoria, Australia. The prevalence of depressive symptoms was 10.5% (95% CI 9.2,12.0) for males and 21.7% (95% CI 20.3,23.7) for females. Depressive symptoms were associated with factors in all domains, with the strongest associations in the family domain. Strong relationships were found between the number of elevated risk and protective factors and depressive symptoms, maintained after adjusting for substance use. Patterns of associations were similar for users and nonsubstance users. The findings indicate that prevention programs targeting factors for substance use have the potential to impact on depression.

A cross-national comparison of risk and protective factors for adolescent substance use : the United States and Australia

Purpose
To compare risk and protective factors that influence youth substance use in Australia and the United States. The two countries have different policy orientations toward substance use: Australia has adopted harm-reduction policies, and the United States has adopted abstinence-focused polices.

Methods
Cross-sectional survey data were collected from independent samples of adolescents in the states of Maine (N = 16,861; 53% female, 7% Non-white) and Oregon (N = 15,542; 51% female, 24% Non-white) in the United States and Victoria in Australia (N = 8442; 54% Female, 11% Non-white) in 1998 (Maine and Oregon) and 1999 (Victoria). Chi-square tests, t-tests, effect size comparisons, and logistic regression analyses that accounted for age and gender were used to investigate cross-national similarities and differences in: (a) rates of cigarette, alcohol, and marijuana use; (b) levels of risk and protective factors; and (c) magnitudes of associations between risk and protective factors and substance use.

Results
More adolescents in Victoria reported using cigarettes and alcohol, whereas more of the U.S. adolescents reported using marijuana. Exposure to risk and protective factors was generally similar in the cross-national samples. However, adolescents in Maine and Oregon perceived handguns to be more readily available, reported more participation in religious activities, and were higher in sensation-seeking and social skills; and adolescents in Victoria had more favorable attitudes toward drug use and reported community norms and parental attitudes more favorable to drug use. Most of the risk and protective factors were strongly associated with substance use to a similar degree in Victoria, Maine, and Oregon. However, among adolescents in Maine and Oregon peer/individual risk and protective factors associated with social detachment were more strongly related to substance use, and among adolescents in Victoria, family protective factors were less strongly related to alcohol use.

Conclusions
Inter-country influences on youth substance use are generally similar despite different policy directions. Existing differences suggest that the abstinence policy context is associated with higher levels of illicit drug use and stronger relations between individual indicators of social detachment and substance use, whereas the harm reduction policy context is related to more cigarette and alcohol use, possibly from exposure to normative influences that are more tolerant of youth drug use.

Undernutrition during suckling in rats elevates plasma adiponectin and its receptor in skeletal muscle regardless of diet composition : a protective effect?

Objective:
Nutrition during critical periods in early life may increase the subsequent risk of obesity, hypertension and metabolic diseases in adulthood. Few studies have focused on the long-term consequences of poor nutrition during the suckling period on the susceptibility to developing obesity when exposed to a palatable cafeteria-style high-fat diet (CD) after weaning.

Design:
This study examined the impact of early undernutrition, followed by CD exposure, on blood pressure, hormones and genes important for insulin sensitivity and metabolism and skeletal muscle mRNA expression of adiponectin receptor 1 (AdipoR1), carnitine palmitoyl-transferase I (CPT-1), cytochrome c oxidase 4 (COX4) and peroxisome proliferator-activated receptor alpha (PPARalpha). Following normal gestation, Sprague–Dawley rat litters were adjusted to 18 (undernourished) or 12 (control) pups. Rats were weaned (day 21) onto either palatable CD or standard chow.

Results:
Early undernourished rats were significantly lighter than control by 17 days, persisting into adulthood only when animals were fed chow after weaning. Regardless of litter size, rats fed CD had doubled fat mass at 15 weeks of age, and significant elevations in plasma leptin, insulin and adiponectin. Importantly, undernutrition confined to the suckling period, elevated circulating adiponectin regardless of post-weaning diet. Blood pressure was reduced in early undernourished rats fed chow, and increased by CD. Early undernutrition was associated with long-term elevations in the expression of AdipoR1, CPT-1, COX4 and PPARalpha in skeletal muscle.

Conclusion:
This study demonstrates the important role of early nutrition on body weight and metabolism, suggesting early undernourishment enhances insulin sensitivity and fatty-acid oxidation. The long-term potential benefit of limiting nutrition in the early postnatal period warrants further investigation.

Nanoparticle coatings for UV protective textiles

As the intensity of UV radiation increases every year, effective methods to block UV rays to protect human skin, plastics, timber and other polymer materials are urgently sought. Textiles serve as important materials for UV protection in many applications. The utilisation of nanoparticles to textile materials has been the object of several studies aimed at producing finished fabrics with different performances. This article reviews the recent advancement in the field of UV blocking textiles and fibers that are functionalised with nanostructured surface coatings. Different types of UV blocking agents are discussed and various examples of UV blocking textiles utilising ZnO and TiO₂ are presented. Future challenges such as wash-fastness and photocatalysis are also discussed.