Role of circumventricular organs in pro-inflammatory cytokine-induced activation of the hypothalamic-pituitary-adrenal axis

1. The past 15 years has seen the emergence of a new field of neuroscience research based primarily on how the immune system and the central nervous system can interact. A notable example of this interaction occurs when peripheral inflammation, infection or tissue injury activates the hypothalamic- pituitary-adrenal axis (HPA). 2. During such assaults, immune cells release the pro- inflammatory cytokines interleukin (IL)-1, IL-6 and tumour necrosis factor-alpha into the general circulation. 3. These cytokines are believed to act as mediators for HPA axis activation. However, physical limitations of cytokines impede their movement across the blood-brain barrier and, consequently, it has been unclear as to precisely how and where IL-1beta signals cross into the brain to trigger HPA axis activation. 4. Evidence from recent anatomical and functional studies suggests two neuronal networks may be involved in triggering HPA axis activity in response to circulating cytokines. These are catecholamine cells of the medulla oblongata and the circumventricular organs (CVO). 5. The present paper examines the role of CVO in generating HPA axis responses to pro-inflammatory cytokines and culminates with a proposed model based on cytokine signalling primarily involving the area postrema and catecholamine cells in the ventrolateral and dorsal medulla.

The effect of musculoskeletal pain on motor activity and control

Aberrant movement patterns and postures are obvious to clinicians managing patients with musculoskeletal pain. However, some changes in motor function that occur in the presence of pain are less apparent. Clinical and basic science investigations have provided evidence of the effects of nociception on aspects of motor function. Both increases and decreases in muscle activity have been shown, along with alterations in neuronal control mechanisms, proprioception, and local muscle morphology. Various models have been proposed in an attempt to provide an explanation for some of these changes. These include the vicious cycle and pain adaptation models. Recent research has seen the emergence of a new model in which patterns of muscle activation and recruitment are altered in the presence of pain (neuromuscular activation model). These changes seem to particularly affect the ability of muscles to perform synergistic functions related to maintaining joint stability and control. These changes are believed to persist into the period of chronicity. This review shows current knowledge of the effect of musculoskeletal pain on the motor system and presents the various proposed models, in addition to other shown effects not covered by these models. The relevance of these models to both acute and chronic pain is considered. It is apparent that people experiencing musculoskeletal pain exhibit complex motor responses that may show some variation with the time course of the disorder. (C) 2001 by the American Pain Society.

Heritability and gene-environment interactions for melanocytic nevus density examined in a U.K. adolescent twin study

Risk factors for melanoma include environmental (particularly ultraviolet exposure) and genetic factors. In rare families, susceptibility to melanoma is determined by high penetrance mutations in the genes CDKN2A or CDK4, with more common, less penetrant genes also postulated. A further, potent risk factor for melanoma is the presence of large numbers of melanocytic nevi so that genes controlling nevus phenotype could be such melanoma susceptibility genes. A large Australian study involving twins aged 12 y of predominantly U.K. ancestry showed strong evidence for genetic influence on nevus number and density. We carried out essentially the same study in the U.K. to gain insight into gene-environment interactions for nevi. One hundred and three monozygous (MZ) and 118 dizygous (DZ) twin pairs aged 10-18 y were examined in Yorkshire and Surrey, U.K. Nevus counts were, on average, higher in boys (mean = 98.6) than girls (83.8) (p = 0.009) and higher in Australia (110.4) than in the U.K. (79.2, adjusted to age 12 y, p < 0.0001), and nevus densities were higher on sun-exposed sites (92 per m(2)) than sun-protected sites (58 per m(2)) (p < 0.0001). Correlations in sex and age adjusted nevus density were higher in MZ pairs (0.94, 95% CI 0.92-0.96) than in DZ pairs (0.61, 95%CI 0.49-0.72), were notably similar to those of the Australian study (MZ = 0.94, DZ = 0.60), and were consistent with high heritability (65% in the U.K., 68% in Australia). We conclude that emergence of nevi in adolescents is under strong genetic control, whereas environmental exposures affect the mean number of nevi.

Least-Cost Planning and electricity industry reform in Australia

Least-Cost Planning played a key role in the development of the energy efficiency and renewable energy industries in the USA, It has not been widely used elsewhere, largely due to differences in other nations' regulatory environments and the emergence of competitive markets as the dominant paradigm for electricity planning, Least-Cost Planning, however may over valuable insights for creating regulatory framework for competitive electricity markers. This paper examines some lessons which may be extracted from an analysis of the Least-Cost Planning experience in the USA and suggests how these lessons might prove beneficial in guiding Australia's electricity industry reform, This analysis demonstrates how market-based reforms may be flawed if they ignore the history of previous reform processes.

Issues in Australian Foreign Policy January to June 2001

The first half of 2001 saw traditional issues dominating the foreign policy agenda, with both Australia's relationship with the United States and the policy of Asian engagement still holding centre stage. But those old issues generated fresh anxieties. In the United States, the incoming Bush administration displayed a genuine radicalism in its approach to foreign policy, and that raised concerns in many Western capitals — including Canberra — about a new mood of unilateralism in Washington. At the same time, the emergence of the thesis that Australia was becoming a "branch office economy", where key decisions were taken in the capital markets of New York and London, made the government noticeably more cautious and selective in its endorsement of globalisation. Further, the issue of Asian engagement grew steadily more complex: Australian policy-makers searched unsuccessfully for a new focus for the policy of Asian engagement, as Japan's economy wallowed and Indonesia's democratic government tottered.

Effect of body size on fecundity of Childers canegrub, Antitrogus parvulus Britton (Coleoptera : Scarabaeidae)

Actual and potential fecundity for Childers canegrub, Antitrogus parvulus Britton, was influenced by the size of females, with the largest females laying the most eggs. Actual or realised fecundity for A. parvulus averaged 18 eggs per female, about half of potential fecundity. Actual fecundity was significantly related to elytron length in a group of laboratory-reared beetles, but not for a group of field-collected beetles. Size was related to potential fecundity for four out of four groups of females collected from emergence traps in the field and for one of two groups reared in the laboratory from field-collected late-instar larvae. As females lay a single batch of eggs, beetle size may be important in the population dynamics of A. parvulus. Populations of A. parvulus with small beetles are potentially less likely to persist and expand than populations with relatively large females.

A typology of community opportunity and vulnerability in metropolitan Australia

A multivariate model using hierarchical clustering and discriminant analysis is used to identify clusters of community opportunity and community vulnerability across Australia's mega metropolitan regions, Variables used in the model measure aspects of structural economic change, occupational change, human capital, income, unemployment, family/household disadvantage, and housing stress. A nine-cluster solution is used to categorise communities across metropolitan space. Significant between-city variations in the incidence of these clusters of opportunity and vulnerability are apparent, suggesting the emergence of marked differentiation between Australia's mega metropolitan regions in their adjustments to changing economic and social conditions. JEL classification: C49, R11, R12.

The game of leapfrog and the Internet: Developing countries and the information-divide

Recent rapid advances in communication technology have changed global structural patterns and produced new concepts and poles of dynamism in international relations. One such technology, which is increasingly causing a mixed reaction across international boundaries, is that of the Internet. For the first time in history the emergence of the Internet has produced an anarchic power that is capable of influencing individuals, societies and governments on a scale previously unimaginable.

Effectiveness of introduced biocontrol insects on the weed Parthenium hysterophorus (Asteraceae) in Australia

Six species of insects and a rust fungus have been successfully established for biocontrol of the weed Parthenicum hysterophorus L. in Queensland, Australia. Effectiveness of biocontrol insects was evaluated at two properties in Queensland during 1996-97 based on an exclusion experiment using insecticides. Parthenium-infested plots with and without biocontrol insects were sampled at monthly intervals and the impact of biocontrol insects on parthenium at individual plant and whole population levels monitored. Biocontrol insects were more effective at Mt Panorama (central Queensland) than at Plain Creek (north Queensland). At Mt Panorama, the leaf-feeding beetle Zygogramma bicolorata Pallister caused 96% defoliation and the stem-galling moth Epiblema strenuana Walker affected 100% of the plants, resulting in reductions of 90% in weed density, 40% in plant height, and 82% in flower production. Exclusion of biocontrol insects resulted in a 52% increase in seedling emergence and a seven-fold increase in the soil seed bank in the following season. At Plain Creek, E. strenuana was the only prominent agent. It affected 92% of the plants and prevented 32% of plants from producing any flowers, reduced plant height by 40% and flower production by 49%, but did not reduce the plant biomass, weed density or soil seed bank. However, exclusion of biocontrol insects resulted in an eight-fold increase in the soil seed bank in the following season.

Effects of moist chilling and solid matrix priming on germination of loblolly pine (Pinus taeda L.) seeds

Loblolly pine ( Pinus taeda L.) seeds from sources with a mild climate under maritime influence (North Carolina) required shorter moist chilling to achieve maximum germination vigor than seeds from sources with a harsher continental climate (Oklahoma). Solid matrix priming (SMP) for 6 d achieved as much as 60 d of moist chilling to improve rapidity, synchrony and completeness of germination for three of the four families studied. SMP after moist chilling increased the rapidity, synchrony and completeness of germination. The benefit of SMP was greatest for non-stratified seeds and the benefit decreased with length of moist chilling. In general, delaying planting for one week after SMP had minor effects on germination when seeds were kept in the SMP matrix at 4 degreesC. Delayed planting after SMP can increase germination rapidity and synchrony of seeds that have received long moist chilling and reduce the benefit of SMP in non-moist-chilled seeds.

Time of treatment influences the appearance of drug-resistant parasites in Plasmodium falciparum infections

A deterministic mathematical model which predicts the probability of developing a new drug-resistant parasite population within the human host is reported, The model incorporates the host's specific antibody response to PfEMP1, and also investigates the influence of chemotherapy on the probability of developing a viable drug-resistant parasite population within the host. Results indicate that early, treatment, and a high antibody threshold coupled with a long lag time between antibody stimulation and activity, are risk factors which increase the likelihood of developing a viable drug-resistant parasite population. High parasite mutation rates and fast PfEMP1 var gene switching are also identified as risk factors. The model output allows the relative importance of the various risk factors as well as the relationships between them to be established, thereby increasing the understanding of the conditions which favour the development of a new drug-resistant parasite population.

The natural history of Hendra and Nipah viruses

Pteropid bats (flying foxes), species of which are the probable natural host of both Hendra and Nipah viruses, occur in overlapping populations from India to Australia. Ecological changes associated with land use and with animal husbandry practices appear most likely to be associated with the emergence of these two agents. (C) 2001 Editions scientifiques et medicales Elsevier SAS.

Emerging pathways in colorectal-cancer development

The past decade has seen the emergence of new pathways in the development of colorectal cancer. There is now clear evidence that subsets of these tumours do not show chromosomal instability and do not follow the suppressor pathway. Instead, about 15% of colorectal cancers are characterised by microsatellite instability (MSI). This feature arises through defective DNA mismatch repair, which is related either to a germline mutation (as in hereditary non-polyposis colorectal carcinoma) or to failure to express a mismatch-repair gene. CpG-island methylation has been linked to sporadic cancers with a high frequency of MSI. This type of methylation leads to loss of gene expression when it occurs in the promoter region of a gene. Tumours may have high or low type C (cancer-related) CpG-island methylation. When methylation affects hMLH1 (mismatch repair gene), the resultant cancer has high MSI.

Pea rms6 mutants exhibit increased basal branching

Our studies on two branching mutants of pea (Pisum sativum L.) have identified a further Ramosus locus, Rms6, with two recessive or partially recessive mutant alleles: rms6-1 (type line S2-271) and rms6-2 (type line K586). Mutants rms6-1 and rms6-2 were derived from dwarf and tall cultivars, Solara and Torsdag, respectively. The rms6 mutants are characterized by increased branching from basal nodes. In contrast, mutants rms1 through rms5 have increased branching from both basal and aerial (upper stem) nodes. Buds at the cotyledonary node of wild-type (WT) plants remain dormant but in rms6 plants these buds were usually released from dormancy. Their growth was either subsequently inhibited, sometimes even prior to emergence above ground, or they grew into secondary stems. The mutant phenotype was strongest for rms6-1 on the dwarf background. Although rms6-2 had a weak single-mutant phenotype, the rms3-1 rms6-2 double mutant showed clear transgression and an additive branching phenotype, with a total lateral length almost 2-fold greater than rms3-1 and nearly 5-fold greater than rms6-2 . Grafting studies between WT and rms6-1 plants demonstrated the primary action of Rms6 may be confined to the shoot. Young WT and rms6-1 shoots had similar auxin levels, and decapitated plants had a similar magnitude of response to applied auxin. Abscisic acid levels were elevated 2-fold at node 2 of young rms6-1 plants. The Rms6 locus mapped to the R to Gp segment of linkage group V (chromosome 3). The rms6 mutants will be useful for basic research and also have possible agronomical value.

Atom lasers, coherent states, and coherence II. Maximally robust ensembles of pure states

As discussed in the preceding paper [Wiseman and Vaccaro, preceding paper, Phys. Rev. A 65, 043605 (2002)], the stationary state of an optical or atom laser far above threshold is a mixture of coherent field states with random phase, or, equivalently, a Poissonian mixture of number states. We are interested in which, if either, of these descriptions of rho(ss) as a stationary ensemble of pure states, is more natural. In the preceding paper we concentrated upon the question of whether descriptions such as these are physically realizable (PR). In this paper we investigate another relevant aspect of these ensembles, their robustness. A robust ensemble is one for which the pure states that comprise it survive relatively unchanged for a long time under the system evolution. We determine numerically the most robust ensembles as a function of the parameters in the laser model: the self-energy chi of the bosons in the laser mode, and the excess phase noise nu. We find that these most robust ensembles are PR ensembles, or similar to PR ensembles, for all values of these parameters. In the ideal laser limit (nu=chi=0), the most robust states are coherent states. As the phase noise or phase dispersion is increased through nu or the self-interaction of the bosons chi, respectively, the most robust states become more and more amplitude squeezed. We find scaling laws for these states, and give analytical derivations for them. As the phase diffusion or dispersion becomes so large that the laser output is no longer quantum coherent, the most robust states become so squeezed that they cease to have a well-defined coherent amplitude. That is, the quantum coherence of the laser output is manifest in the most robust PR ensemble being an ensemble of states with a well-defined coherent amplitude. This lends support to our approach of regarding robust PR ensembles as the most natural description of the state of the laser mode. It also has interesting implications for atom lasers in particular, for which phase dispersion due to self-interactions is expected to be large.