Long lived multi-isotype anti-HIV antibody responses following a prime-double boost immunization strategy

Despite decades of work, an effective HIV vaccine remains elusive. In an effort to elicit protective immunity, investigators have sought to define vaccines able to elicit durable HIV-specific B-cell and T-cell activities. Additionally, vaccines are sought which can induce antibodies of a variety of isotypes, as each isotype possesses unique attributes in terms of opsonization, Fc receptor binding capacity, complement fixation and location. One prominent new vaccine strategy, applied to numerous distinct antigenic systems is the prime boost-regimen, with DNA, vaccinia virus (VV), and/or purified recombinant protein. To examine the durability, location and isotype distribution of responses induced by prime-boost regimens, we tested successive immunizations with DNA, VV and protein (D-V-P), comparing three forms of protein inoculations: (i) purified protein administered intramuscularly with complete Freunds adjuvant, (ii) purified protein administered intranasally, and (iii) purified protein conjugated to oxidized mannan, administered intranasally. We found that all three protocols elicited serum antibodies of multiple isotypes, with serum IgA being most prominent among mice immunized with mannan-conjugated protein. All D-V-P protocols, regardless of protein form or route, also elicited antibody responses at mucosal surfaces. In bronchoalveolar lavage, a tendency toward IgA production was again most prominent in mice boosted with the protein–mannan conjugate. Both B-cell and T-cell responses were sustained for more than 1 year post-immunization following each form of vaccination. Contemporaneous with long-lasting serum and mucosal antibodies were antibody forming cells in the bone marrow of primed animals. Results highlight the D-V-P vaccination strategy as a promising approach for attaining durable, multi-isotype B-cell and T-cell activities toward HIV.

Frederick McCoy and the Phylum Brachiopoda

Sir Frederick McCoy, during a long career involved with taxonomy, contributed extensively to the knowledge of the fossil record of the Phylum Brachiopoda, From his classic early monographs on the fossil faunas of the Carboniferous and Silurian of Ireland, to his later works in Victoria where important new species were described and illustrated, McCoy demonstrated the same care, meticulous rigour and quality of illustrations that typified all his work. His contributions on the Brachiopoda are of high and long-lasting significance but form only part of his much broader contribution to palaeontology.

Strategies which aim to positively impact on weight, physical activity, diet and sedentary behaviours in children from zero to five years. A systematic review of the literature

Preventing the development of obesity in children is an international health priority. To assess the effectiveness of interventions designed to prevent obesity, promote healthy eating and/or physical activity and/or to reduce sedentary behaviours in 0–5-year-old children, a systematic review of the literature was performed. Literature searches were limited to articles published between January 1995 and June 2006, printed in English and sampling children aged 0–5-years. Searches excluded literature concerned with breastfeeding, eating disorders, and interventions which were school-based or concerned with obesity treatment. Two reviewers independently extracted data and assessed study strengths and weaknesses. Nine included studies were grouped based on the settings in which they were delivered. Most studies involved multi-approach interventions, were conducted in the USA and varied in study designs and quality. All showed some level of effectiveness on at least one obesity-behaviour in young children. These studies support, at a range of levels, the premise that parents are receptive to and capable of some behavioural changes that may promote healthy weight in their young children. The small quantity of research heralds the need, particularly given the potential for early intervention to have long-lasting impacts on individual and population health, to build in a substantial way upon this evidence base.

Interactions and networks in Australian tourism

There are many participants in the tourism network who have vested interests in tourism development. These organizations include hotels, associations of hotels and hotel owners, inbound travel agents, travel wholesalers, tourism industry associations, airlines, cruise lines, tourism promotional agencies, regional and local tourism authorities, SME tourism businesses, conference and convention centres and many more. Individuals in the tourism industry intermittently change employment. They often remain in the industry and can move between types of organizations. Their contacts, associations and personal networks remain useful and indeed are utilized. The Interactive Approach postulated by the IMP Group proposes that both suppliers and manufacturers are often involved in close, long-lasting adaptive relationships. Firms within relationships must work together, share objectives, share information and also communicate clearly and precisely using a common language. Here relationship partners should have a similar point of view on the meaning of marketing strategy and related concepts including market segmentation, differentiation and competitive positioning.

This paper seeks to assess the nature, perspectives and characteristics of interactions in the tourism network in Australia. There are two stages of this research. The first stage obtained the perspectives of network participants on the challenges facing tourism, key growth segments, brand and promotional strategies and customer insights and satisfaction levels. Participants were also asked to provide advice to the national marketing organization on a range of developmental topics. The second stage of this research assesses the interaction patterns among network participants Network picture, network position, resource constellations, interaction, resources and activities, interdependence, adaptation, actor bonds, strategy and change are also assessed. The relationships are political and consultative in nature. There is much interdependence and possible conflict between the network participants. The national tourism body has particular skills in tourism planning and tourism research. They also have significant resources and the ability to influence inbound tourism patterns. This paper seeks to assess and understand the interactions within this network.

Does monetary policy matter in a less developed economy? Evidence from Bangladesh

This paper explores the role of monetary policy in the context of a less developed economy. Monetary transmission mechanisms in less developed economies can be quite different from an industrialized economy, as unlike industrialized countries, these economies are characterized by the small size of organized financial markets, limited substitutability between money and other assets and weak fiscal and monetary institutions. We utilize the Structural VAR approach to analyze the monetary transmission process and impacts of monetary policy on different macro variables in Bangladesh. Monetary policy shocks are identified using non-recursive contemporaneous restrictions, which are based on the Central Bank's reaction function and the structure of the economy. We found strong evidence for the interest rate channel of monetary policy in Bangladesh. Our findings indicate that monetary policy shocks are important sources of fluctuations in the rate of interest, output and prices. Expansionary monetary policies are found to be harmful for achieving price stability in Bangladesh, as they not only increase the prices permanently, but also make the price level more volatile. We also found the evidence of a long lasting effect of monetary policy on output, which suggests that contractionary policy measures may create sustained recession in Bangladesh.

Late palaeozoic global changes affecting high-latitude environments and biotas : an introduction

The Late Palaeozoic Ice Age (LPIA), spanning approximately from ~320 Ma (Serpukhovian, late Mississippian) to 290 Ma (mid-Sakmarian, Early Permian), represents the vegetated Earth’s largest and most long-lasting regime of severe and multiple glaciations, involving processes and patterns probably comparable to those of the Last Ice Age. Accompanying the LPIA occurred a number of broadly synchronous global environmental and biotic changes. These global changes, as briefly reviewed and summarized in this introductory paper, comprised (but are not limited to) the following: massive continental reorganization in the lead up to the final assembly of Pangea resulting in profound changes in global palaeogeography, palaeoceanography and palaeobiogeogarphy; substantially lowered global atmospheric carbon dioxide concentrations (pCO₂), coupled with an unprecedented increase in atmospheric oxygen concentrations reaching Earth's all-time high in its last 600 million year history; sharp global temperature and sea-level drops (albeit with considerable spatial and temporal variability throughout the ice age); and apparently a prolonged period of global sluggish macro-evolution with both low extinction and origination rates compared to other times. In the aftermath of the LPIA, the world's climate entered into a transitional climate phase through the late Early to Middle Permian before its transformation into a greenhouse state towards the end-Permian. In recent years, considerable amount of data and interpretations have been published concerning the physical evidence in support of the LPIA, its broad timeframe and eustatic and ecosystem responses from the lower latitudes, but relatively less attention has been drawn to the impact of the ice age on late Palaeozoic high-latitude environments and biotas. It is with this mission in mind that we have organized this special issue, with the central focus on late Palaeozoic high latitude regions of both hemispheres, that is, Gondwana and northern Eurasia. Our aim is to gather a set of papers that not only document the physical environmental changes that had occurred in the polar regions of Gondwana and northern Eurasia during the LPIA, but also review on the biotic responses at different taxonomic, ecological and spatial scales to these physical changes in a refined chronological timeframe.

This introductory paper is designed to provide a global context for the special issue, with a brief review of key late Palaeozoic global environmental changes (including: changes in global land-sea configurations, atmospheric chemistry, global climate regimes, global ocean circulation patterns and sea levels) and large -scale biotic (biogeographic and evolutionary) responses, followed by a summary of what we see as unresolved scientific issues and various working hypotheses concerning late Palaeozoic global changes and, in particular, the LPIA, as a possible reference to future research.

Arresting the decline in senior school chemistry

Enrolments in Australian Year 11 and year 12 chemistry are declining. In 1992, 23% of Australian year 12 students studied chemistry, decreasing to 18% in 2010. For science as a whole, the decrease is even more dramatic, from 94% to 51%. The decrease is slowing, but is continuing.
How should we respond to the report? Firstly, we should realise that it is not all gloom and doom. Secondly, education is not solely the responsibility of curriculum authorities and teachers. Each RACI member can communicate, inform and generally educate the wider community about the excitement and value of chemical science. Just a couple of hours of your time is not a panacea, but it can still make long-lasting impacts and affect career choices: even the largest beach consists of tiny individual grains of sand.

Short-term exercise training early in life restores deficits in pancreatic B-cell mass associated with growth restriction in adult male rats

Fetal growth restriction is associated with reduced pancreatic ß-cell mass, contributing to impaired glucose tolerance and diabetes. Exercise training increases ß-cell mass in animals with diabetes and has long-lasting metabolic benefits in rodents and humans. We studied the effect of exercise training on islet and ß-cell morphology and plasma insulin and glucose, following an intraperitoneal glucose tolerance test (IPGTT) in juvenile and adult male Wistar-Kyoto rats born small. Bilateral uterine vessel ligation performed on day 18 of pregnancy resulted in Restricted offspring born small compared with shamoperated Controls and also sham-operated Reduced litter offspring that had their litter size reduced to five pups at birth. Restricted, Control, and Reduced litter offspring remained sedentary or underwent treadmill running from 5 to 9 or 20 to 24 wk of age. Early life exercise increased relative islet surface area and ß-cell mass across all groups at 9 wk, partially restoring the 60–68% deficit (P = 0.05) in Restricted offspring. Remarkably, despite no further exercise training after 9 wk, ß-cell mass was restored in Restricted at 24 wk, while sedentary littermates retained a 45% deficit (P = 0.05) in relative ß-cell mass. Later exercise training also restored Restricted ß-cell mass to Control levels. In conclusion, early life exercise training in rats born small restored ß-cell mass in adulthood and may have beneficial consequences for later metabolic health and disease.

Human brain structural change related to acute single exposure to sarin

Objective This study aimed to identify persistent morphological changes subsequent to an acute single-time exposure to sarin, a highly poisonous organophosphate, and the neurobiological basis of long-lasting somatic and cognitive symptoms in victims exposed to sarin.

Methods Thirty-eight victims of the 1995 Tokyo subway sarin attack, all of whom had been treated in an emergency department for sarin intoxication, and 76 matched healthy control subjects underwent T1-weighted and diffusion tensor magnetic resonance imaging (DTI) in 2000 to 2001. Serum cholinesterase (ChE) levels measured immediately and longitudinally after the exposure and the current severity of chronic reports in the victims were also evaluated.

Results The voxel-based morphometry exhibited smaller than normal regional brain volumes in the insular cortex and neighboring white matter, as well as in the hippocampus in the victims. The reduced regional white matter volume correlated with decreased serum cholinesterase levels and with the severity of chronic somatic complaints related to interoceptive awareness. Voxel-based analysis of diffusion tensor magnetic resonance imaging further demonstrated an extensively lower than normal fractional anisotropy in the victims. All these findings were statistically significant (corrected p < 0.05).

Interpretation Sarin intoxication might be associated with structural changes in specific regions of the human brain, including those surrounding the insular cortex, which might be related to elevated subjective awareness of internal bodily status in exposed individuals.

Effect of deep brain stimulation on nucleus accumbens dopamine in a preclinicla model of antidepressant treatment-resistance

Background / Purpose: To determine if clinically effective deep brain stimulation (DBS) of neurosurgical targets for treatment-resistant depression regulates transient mesoaccumbens dopamine release in control and antidepressant-resistant animals (rats).

Main conclusion: In control rats, DBS stimulation of either the nucleus accumbens or infralimbic cortex significantly attenuated transient mesoaccumbens dopamine efflux, with nucleus accumbens DBS inducing a greater attenuation than infralimbic DBS. High frequency DBS of both targets induced long-term depression of transient accumbens dopamine release, lasting > 2hr post DBS.

Conversely, in antidepressant-resistant rats, infralimbic DBS significantly potentiated transient mesoaccumbens dopamine efflux during stimulation, but failed to induce long-lasting changes in neurotransmission. This suggests that a key mechanism of DBS for treatment-resistant depression is the regulation of dysfunctional mesoaccumbens dopamine neurotransmission.

Advancing science and policy through a coordinated international study of physical activity and built environments: IPEN Adult methods

Background: National and international strategies to increase physical activity emphasize environmental and policy changes that can have widespread and long-lasting impact. Evidence from multiple countries using comparable methods is required to strengthen the evidence base for such initiatives. Because some environment and policy changes could have generalizable effects and others may depend on each country’s context, only international studies using comparable methods can identify the relevant differences. Methods: Currently 12 countries are participating in the International Physical Activity and the Environment Network (IPEN) study. The IPEN Adult study design involves recruiting adult participants from neighborhoods with wide variations in environmental walkability attributes and socioeconomic status (SES). Results: Eleven of twelve countries are providing accelerometer data and 11 are providing GIS data. Current projections indicate that 14,119 participants will provide survey data on built environments and physical activity and 7145 are likely to provide objective data on both the independent and dependent variables. Though studies are highly comparable, some adaptations are required based on the local context. Conclusions: This study was designed to inform evidence-based international and country-specific physical activity policies and interventions to help prevent obesity and other chronic diseases that are high in developed countries and growing rapidly in developing countries.

Tribes and political representation: the case of post-war Iraq

 Ten years have passed since the US-led invasion of Iraq in 2003, and the political scene in Iraq is still blurry. Iraq was promoted to be the democratic example in the Middle East. The US came to Iraq to “create” a democratic system that can be a model for other countries in the region. A major factor in creating such environment is by changing the radical centralised totalitarian regime with a weak state that can give more space to building the civil society in new Iraq (Looney, 2003). Nonetheless, the socio-economic and political indicators of the newly installed political “democratic” system point to notable failures. Apart from poor socio-economic factors, the new political elite has either misused democracy for personal, ethno-sectarian or partisan gains or abused the system to ensure their long lasting presence in the decision making arena. Corruption, disconnection from electorate, poor performance and carelessness of politicians and failing state service provisions have all made citizens question the feasibility of political participation in elections. The electorate seem to have lesser faith in the political parties and blocs whose legitimacy of representation  is at stake. Noticeably, tribes have stepped forward to mobilise people as a non-partisan and independent powerful social structure. They have been active in lobbying the state as well as encouraging their members for active participation. This paper discusses the extent to which Iraqi tribes are involved in political participation. It explores their roles in active citizenship and the way they represent and mobilise their  members. It also probes whether tribes have the influence on shaping the political trajectory in Iraq.

A review of migratory behaviour of sea turtles off southeastern Africa

The survival of sea turtles is threatened by modern fishing methods, exploitation of eggs and habitat destruction. Forming keystone species in the ocean, their extinction would disrupt the marine food chain in ways as yet unknown. The Indian Ocean has many breeding areas for sea turtles, the southernmost ones being on the Maputaland coast of KwaZulu-Natal, where loggerhead and leatherback turtles nest in large numbers thanks to long-lasting protection programmes. For the leatherback this is the only known nesting site in the entire western Indian Ocean. At the end of the reproductive season, both loggerheads and leatherbacks undertake migrations towards disparate feeding areas. To contribute to their conservation, the migratory behaviour of these animals needs to be understood. Here we review 10 years studying this behaviour using transmitters that telemeter data via satellite. It emerges that these species frequent widely dispersed areas ranging from the Atlantic Ocean to the Mozambique Channel. The migratory behaviour of leatherback and loggerhead turtles is, however, very different, probably due to their differing food requirements. While loggerhead postnesting movements have a truly migratory nature, the large-scale wanderings of leatherbacks are better described as prolonged sojourns in extended feeding areas.

Characterization of zebrafish polymerase iii promoters for the expression of short hairpin RNA interference molecules

RNA interference (RNAi) is a powerful, sequence specific, and long-lasting method of gene knockdown, and can be elicited by the expression of short-hairpin RNA (shRNA) molecules driven via polymerase III type 3 promoters from a DNA vector or transgene. To further develop RNAi as a tool in zebrafish, we have characterized the zebrafish U6 and H1 snRNA promoters and compared the efficiency of each of the promoters to express an shRNA and silence a reporter gene, relative to previously characterized U6 promoters from pufferfish, chicken, and mouse. Our results show that the zebrafish polymerase III promoters were capable of effective gene silencing in the zebrafish ZF4 cell line, but were ineffective in mammalian Vero cells. In contrast, mouse and chicken promoters were active in Vero but not ZF4 cells, highlighting the importance of homologous promoters to achieve effective silencing.

Promising pre-clinical validation of targeted radionuclide therapy using a [131I] labelled iodoquinoxaline derivative for an effective melanoma treatment

Targeted internal radionuclide therapy (TRT) would be an effective alternative to current therapies for dissemi- nated melanoma treatment. At our institution, a class of iodobenzamides has been developed as potent melanoma- seeking agents. This review described the preclinical vali- dations of a quinoxaline derivative molecule (ICF01012) as tracer for TRT application. It was selected for its high, specific and long-lasting uptake in tumour with rapid clear- ance from non-target organs providing suitable dosimetry parameters for TRT. Extended in vivo study of metabolic profiles confirmed durable tumoural concentration of the unchanged molecule form. Moreover melanin specificity of ICF01012 was determined by binding assay with syn- thetic melanin and in vivo by SIMS imaging. Then, we showed in vivo that [131I] ICF01012 treatment drastically inhibited growth of B16F0, B16Bl6 and M4Beu tumours whereas [131I] NaI or unlabelled ICF01012 treatment was without significant effect. Histological analysis showed that residual tumour cells exhibit a significant loss of aggres- siveness after treatment. This anti-tumoural effect was associated with a lengthening of the treated-mice survival time and an inhibition of lung dissemination for B16Bl6 model. Results presented here support the concept of TRT using a [131I] labelled iodoquinoxaline derivative for an effective melanoma treatment.