Comparison of taurine- and glycine-induced conformational changes in the M2-M3 domain of the glycine receptor

In the ionotropic glutamate receptor, the global conformational changes induced by partial agonists are smaller than those induced by full agonists. However, in the pentameric ligand-gated ion channel receptor family, the structural basis of partial agonism is not understood. This study investigated whether full and partial agonists induce different conformation changes in the glycine receptor chloride channel ( GlyR). A substituted cysteine accessibility analysis demonstrated previously that glycine binding induced an increase in surface accessibility of all residues from Arg(271) to Lys(276) in the M2-M3 domain of the homomeric alpha1 GlyR. Here we compare the surface accessibility changes induced by the full agonist, glycine, and the partial agonist, taurine. In GlyRs incorporating the A272C, S273C, L274C, or P275C mutation, the reaction rate of the cysteine-specific compound, methanethiosulfonate ethyltrimethylammonium, depended on how strongly the receptors were activated but was agonist-independent. Reaction rates could not be compared in the R271C and K276C mutant GlyRs because methanethiosulfonate ethyltrimethylammonium did not modify the extremely small currents induced by saturating taurine or equivalent low glycine concentrations. The results indicate that bound taurine and glycine molecules impose identical conformational changes to the M2-M3 domain. We therefore conclude that the higher efficacy of glycine is due to an increased ability to stabilize a common activated configuration.

Ventilatory changes following head-up tilt and standing in healthy subjects

Passive tilting increases ventilation in healthy subjects; however, controversy surrounds the proposed mechanism. This study is aimed to evaluate the possible mechanism for changes to ventilation following passive head-up tilt (HUT) and active standing by comparison of a range of ventilatory, metabolic and mechanical parameters. Ventilatory parameters (V (T), V (E), V (E)/VO2, V (E)/VCO2, f and PetCO(2)), functional residual capacity (FRC), respiratory mechanics with impulse oscillometry; oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured in 20 healthy male subjects whilst supine, following HUT to 70 degrees and unsupported standing. Data were analysed using a linear mixed model. HUT to 70 degrees from supine increased minute ventilation (V (E)) (P < 0.001), tidal volume (V (T)) (P=0.001), ventilatory equivalent for O-2 (V (E)/VO2) (P=0.020) and the ventilatory equivalent for CO2 (V (E)/VCO2) (P < 0.001) with no change in f (P=0.488). HUT also increased FRC (P < 0.001) and respiratory system reactance (X5Hz) (P < 0.001) with reduced respiratory system resistance (R5Hz) (P=0.004) and end-tidal carbon dioxide (PetCO(2)) (P < 0.001) compared to supine. Standing increased V (E) (P < 0.001), V (T) (P < 0.001) and V (E)/VCO2 (P=0.020) with no change in respiratory rate (f) (P=0.065), V (E)/VO2 (P=0.543). Similar changes in FRC (P < 0.001), R5Hz (P=0.013), X5Hz (P < 0.001) and PetCO(2) (P < 0.001) compared to HUT were found. In contrast to HUT, standing increased VO2 (P=0.002) and VCO2 (P=0.048). The greater increase in V (E) in standing compared to HUT appears to be related to increased VO2 and VCO2 associated with increased muscle activity in the unsupported standing position. This has implications for exercise prescription and rehabilitation of critically ill patients who have reduced cardiovascular and respiratory reserve.

Remunerating private psychiatrists for participating in case conferences

ABSTRACT : BACKGROUND : On 1 November 2000, a series of new item numbers was added to the Medicare Benefits Schedule, which allowed for case conferences between physicians (including psychiatrists) and other multidisciplinary providers. On 1 November 2002, an additional set of numbers was added, designed especially for use by psychiatrists. This paper reports the findings of an evaluation of these item numbers. RESULTS : The uptake of the item numbers in the three years post their introduction was low to moderate at best. Eighty nine psychiatrists rendered 479 case conferences at a cost to the Health Insurance Commission of $70,584. Psychiatrists who have used the item numbers are generally positive about them, as are consumers. Psychiatrists who have not used them have generally not done so because of a lack of knowledge, rather than direct opposition. The use of the item numbers is increasing over time, perhaps as psychiatrists become more aware of their existence and of their utility in maximising quality of care. CONCLUSION : The case conferencing item numbers have potential, but as yet this potential is not being realised. Some small changes to the conditions associated with the use of the item numbers could assist their uptake.

Symptom reporting and associations with compensation status, self-awareness, causal attributions, and emotional wellbeing following traumatic brain injury

Individuals seeking compensation following traumatic brain injury (TBI) are often found to report a disproportionately high level of symptoms relative to objective indicators of impairment. Previous studies highlight that level of symptom reporting is also related to self-awareness, causal attribution, and emotional wellbeing. Therefore, the reasons for high symptom reporting in the context of compensation are generally unclear. This study aimed to identify whether self-awareness, causal attribution, and emotional wellbeing are significantly associated with level of symptom reporting after controlling for compensation status. A sample of 54 participants with TBI comprised two groups, namely, claimants (n = 27) and non-claimants (n = 27), who were similar in terms of demographic and neuro-cognitive variables. Participants completed the Symptom Expectancy Checklist, Hospital Anxiety Depression Scale, Awareness Questionnaire and a causal attribution scale. A series of independent t tests and Pearson's correlations identified that a higher level of symptom reporting was associated with the following: seeking compensation, less severe TBI, increased age, greater self-awareness, increased post-injury changes reported by relatives, a higher level of mood symptoms, and a tendency to blame other people. Multivariate analysis identified that after controlling for demographic, injury, and compensation status variables, level of mood symptoms and self-awareness were significantly associated with level of symptom reporting. The findings suggest that mood symptoms and heightened self-awareness are significantly related to high symptom reporting independent of compensation status, thus supporting the need for clinicians to interpret symptom reporting within a biopsychosocial context.

Phototrophic microendoliths bloom during coral "white syndrome"

Following rapid lesion progression of white syndrome in tabular Acropora spp., the white bare skeleton gradually changes to green, a result of endolithic algae blooms (primarily Ostreobium spp.). Endolithic algal biomass and chlorophyll concentration were found to be an order of magnitude higher in the green zone compared with healthy appearing parts of each colony. Chl b to Chl a ratio increased from 1:1.6 in the healthy area to 1:2 and 1:3.5 in the white exposed skeleton and green zones, respectively. These observations together with pulse amplitude modulated (PAM) fluorometry suggest photoacclimation of the endoliths in the green zone. Histopathological microscopy revealed that the endolithic algal filaments penetrate the coral tissue. This study highlights the interaction of endolithic algae with both the skeleton and host tissue. This may have a critical role in the processes that accompany the post-disease state in reef-building corals.

The complexity of p53 stabilization and activation

A number of proteins are activated by stress stimuli but none so spectacularly or with the degree of complexity as the tumour suppressor p53 (human p53 gene or protein). Once stabilized, p53 is responsible for the transcriptional activation of a series of proteins involved in cell cycle control, apoptosis and senescence. This protein is present at low levels in resting cells but after exposure to DNA-damaging agents and other stress stimuli it is stabilized and activated by a series of post-translational modifications that free it from MDM2 (mouse double minute 2 but used interchangeably to denote human also), a ubiquination ligase that ubiquitinates it prior to proteasome degradation. The stability of p53 is also influenced by a series of other interacting proteins. In this review, we discuss the post-translational modifications to p53 in response to different stresses and the consequences of these changes.

Distance measurement using the change in junction voltage across a laser diode due to the self-mixing effect

Conventional detection scheme for self-mixing sensors uses an integrated photodiode within the laser package to monitor the self mixing signal. This arrangement can be simplified by directly obtaining the self-mixing signals across the laser diode itself and omitting the photodiode. This work reports on a Vertical-Cavity Surface-Emitting Laser (VCSEL) based selfmixing sensor using the laser junction voltage to obtain the selfmixing signal. We show that the same information can be obtained with only minor changes to the extraction circuitry leading to potential cost saving with reductions in component costs and complexity and significant increase in bandwidth favoring high speed modulation. Experiments using both photo current and voltage detection were carried out and the results obtained show good agreement with the theory.

Microsensors technology used to measure productivity and other biochemical processes in the upper regions of aquatic sediments

Carbonate sediments are dynamic three-dimensional environments where the surface layers are constantly moving and mixing due to the energy of the water column. It is also an environment of dynamic biological, chemical and physical interaction and modification. The biological community can actively influence changes to sediment characteristics and associated biochemistry. Bioturbation resulting from macrofaunal activity disrupts sediment structure and biochemical arrangements and reduces the critical shear forces required to move sediment particles, adding to the dynamic and complex physical and biogeochemical nature of the sediment. Laboratory studies using both planner optodes and glass needle microsensors were used to measure abiotic sediment characteristics such as the depth distribution and concentrations of PAR. The biochemical nature of coral reef sediment were also investigated, specifically the quantification and the distribution of dissolved oxygen within coarse and fine-grained sediments under regimes of light and darkness. Results highlighted the significant contribution microalgal productivity and bioturbation has on distribution of dissolved oxygen in the upper sediment layers. On the reef flat a shallow water lander system was employed to measure concentrations of O2, pH, S, Ca and temperature over periods of 24 to 48 hours in coarse and fine-grained sediments. Similarities between laboratory and in situ results where evident, however the in situ environment was more dynamic and the distribution and concentrations of dissolved oxygen were more complex and correlated to irradiance, temperature and biological activity. Microsensor technology provides us with the opportunity to study, at very high resolutions, the upper irradiated; photosynthetically active regions of aquatic sediments along with anoxic processes deeper in sub-euphotic regions of the sediments.

Applying a Systems Approach to the Analysis of the Benefits of Conversion to Organic Production

Although the current level of organic production in industrialised countries amounts to little more than 1-2 percent, it is recognised that one of the major issues shaping agricultural output over the next several decades will be the demand for organic produce (Dixon et al. 2001). In Australia, the issues of healthy food and environmental concern contribute to increasing demand and market volumes for organic produce. However, in Indonesia, using more economical inputs for organic production is a supply-side factor driving organic production. For individual growers and processors, conversion from conventional to organic agriculture is often a challenging step, entailing a thorough revision of established practices and heightened market insecurity. This paper examines the potential for a systems approach to the analysis of the conversion process, to yield insights for household and community decisions. A framework for applying farming systems research to investigate the benefits of organic production in both Australia and Indonesia is discussed. The framework incorporates scope for farmer participation, crucial to the understanding of farming systems; analysis of production; and relationships to resources, technologies, markets, services, policies and institutions in their local cultural context. A systems approach offers the potential to internalise the external effects that may be constraining decisions to convert to organic production, and for the design of decision-making tools to assist households and the community. Systems models can guide policy design and serve as a mechanism for predicting the impact of changes to the policy and market environments. The increasing emphasis of farming systems research on community and environment in recent years is in keeping with the proposed application to organic production, processing and marketing issues. The approach will also facilitate the analysis of critical aspects of the Australian production, marketing and policy environment, and the investigation of these same features in an Indonesian context.