Gating charge transfer due to fixed ionizable sites

An alternative origin is suggested for one component of the gating charge transfer that is measured just prior to and during the opening of an ion channel. Rather than it originating solely from the motion of groups with fixed charge, some may stem from ionizable sites which remain fixed in position but change their state of charge. Such changes involve proton migration across the membrane. Two cases are discussed. In the first the ionizable group changes its charge in response to the change in its dielectric environment resulting from the formation of an aqueous pore and in the second the change is as the direct result of the applied trans-membrane voltage. Some of the predicted characteristics of this novel component of gating charge transfer are described.     

Pulmonary aspergillosis and endophthalmitis: complications of Cushing's syndrome.

Ischemic heart disease continues to be the leading cause of death among middle-aged people in industrialized countries. However, in North America the rates of death and disability from coronary artery disease (CAD) have declined, mostly because of a reduction of the main modifiable risk factors (high serum cholesterol levels, smoking and hypertension). Intervention trials have consistently shown that the lowering of the severity of risk factors decreases the incidence of CAD. These studies have introduced the goals of preventive cardiology to clinicians but have not provided the necessary knowledge and skills to achieve them. Unfortunately, with the exception of hypertension, the risk factors for CAD are infrequently assessed and managed in ambulatory patients. Incorporation of detection and intervention strategies derived from recent epidemiologic, behavioural and biomedical research into the existing primary health care system may be the most efficient and effective approach to further reducing the impact of CAD. The family physician''s office is the ideal location to implement behavioural change strategies. However, primary care intervention to decrease the risk of ischemic heart disease among people at high risk has yet to be studied. In addition, whether the same clinicians who render primary care can assume the responsibility for surveillance and preventive care has to be demonstrated.     

Nutritional asymmetries are related to division of labor in a queenless ant

Eusocial species exhibit pronounced division of labor, most notably between reproductive and non-reproductive castes, but also within non-reproductive castes via morphological specialization and temporal polyethism. For species with distinct worker and queen castes, age-related differences in behavior among workers (e.g. within-nest tasks versus foraging) appear to result from physiological changes such as decreased lipid content. However, we know little about how labor is divided among individuals in species that lack a distinct queen caste. In this study, we investigated how fat storage varied among individuals in a species of ant (Dinoponera australis) that lacks a distinct queen caste and in which all individuals are morphologically similar and capable of reproduction (totipotent at birth). We distinguish between two hypotheses, 1) all individuals are physiologically similar, consistent with the possibility that any non-reproductive may eventually become reproductive, and 2) non-reproductive individuals vary in stored fat, similar to highly eusocial species, where depletion is associated with foraging and non-reproductives have lower lipid stores than reproducing individuals. Our data support the latter hypothesis. Location in the nest, the probability of foraging, and foraging effort, were all associated with decreased fat storage.     

Bias Assessment of General Chemistry Analytes using Commutable Samples

Harmonisation of reference intervals for routine general chemistry analytes has been a goal for many years. Analytical bias may prevent this harmonisation. To determine if analytical bias is present when comparing methods, the use of commutable samples, or samples that have the same properties as the clinical samples routinely analysed, should be used as reference samples to eliminate the possibility of matrix effect. The use of commutable samples has improved the identification of unacceptable analytical performance in the Netherlands and Spain. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) has undertaken a pilot study using commutable samples in an attempt to determine not only country specific reference intervals but to make them comparable between countries. Australia and New Zealand, through the Australasian Association of Clinical Biochemists (AACB), have also undertaken an assessment of analytical bias using commutable samples and determined that of the 27 general chemistry analytes studied, 19 showed sufficiently small between method biases as to not prevent harmonisation of reference intervals. Application of evidence based approaches including the determination of analytical bias using commutable material is necessary when seeking to harmonise reference intervals.     

Identification and characterization of IS1 transposition in plasmid amplification mutants of E. coli clones producing DNA vaccines

Merck Research Laboratories has developed a highly productive Escherichia coli fermentation process to produce plasmid DNA for use as vaccines. The process consists of a fed-batch fermentation in a chemically defined medium. Initiation of the feed stream precedes a growth-limited phase in which plasmid DNA is amplified. The fermentation is only maximally productive for a small fraction of E. coli transformants designated as high-producers, while the predominant low-producer population does not amplify plasmid DNA. In experiments undertaken to probe this phenomenon, transposition of the 768-bp E. coli insertion sequence IS1 into an HIV DNA vaccine vector was observed in several low-producer clones. IS1 was found to insert in or near the neomycin resistance gene in nearly a dozen unique sites from within a single population of plasmid molecules. The fraction of IS1-containing plasmids within several clones was determined by quantitative polymerase chain reaction and was found to increase with increasing cultivation time in the chemically defined medium. Because transposition into an antibiotic-resistance gene is unlikely to affect plasmid amplification, the genomes of high- and low-producers of three different HIV DNA vaccine vectors were subsequently profiled by restriction fragment length polymorphism analysis. In all three cases, IS1 insertional mutations were found in the genomes of the predominant low-producers, while the genomes of the high-producers were indistinguishable from untransformed cells. The insertions reside on similarly sized fragments for two of the low-producer clones, and the fragment size is smaller for the third clone. The third clone also produces much less plasmid DNA than a typical low-producer. The results suggest the presence of an IS1 insertional mutation that affects plasmid replication and amplification, possibly in a position-dependent manner.     

Topiramate as a neuroprotectant in a rat model of global ischemia-induced neurodegeneration.

The neuroprotective properties of topiramate were evaluated in a rat model of stroke in which neurodegeneration was induced by temporary global ischemia. In this model, the ischemia resulted from 11 min of cardiac arrest during atraumatic chest compression. Resuscitated rats exhibit a characteristic neurological syndrome characterized by sound-induced convulsions, specific motor and behavioral deficits, and death of hippocampal CA1 pyramidal neurons. Topiramate, when administered i.v. 30 min after resuscitation, reduced the degree of motor impairment (P< 0.05 vs control at doses of 10 and 20 mg/kg) and seizure severity (P< 0.05 vs control at a dose of 10 mg/kg on the fifth recovery day). The highest dose of topiramate (20 mg/kg i.v.) eliminated nearly all histologic signs of hippocampal ischemic neuronal injury (P< 0.001). Phenytoin at 20 mg/kg i.v. exhibited neuroprotectant effects similar to those observed for topiramate at 20 mg/kg i.v.. In normal rats, neither topiramate nor phenytoin at 20 mg/kg i.v. induced any apparent neurological impairment; however, at 40 and 60 mg/kg i.v. both induced a mild impairment typical of most anticonvulsants. The results of this study support the concept that topiramate possesses neuroprotective properties.     

Stock delineation of pink snapper and tailor from Western Australia by analysis of stable isotope and strontium/calcium ratios in otolith carbonate

The ¹⁸O/¹⁶O and ¹³C/¹²C ratios in the otolith carbonate of pink snapper Pagrus auratus and tailor (bluefish) Pomatomus saltatrix, from several locations along the Western Australian coast, indicated that pink snapper stocks are location specific but that tailor stocks are less so. The hypersaline Shark Bay, on the coast of Western Australia, generated strongly characteristic isotopic signatures which serve as natural tags. Otolith carbonate from pink snapper from normal oceanic waters just north of Shark Bay showed no evidence that the fish had been in hypersaline water. Similarly, pink snapper from the hypersaline bay showed no evidence of having spent time at normal oceanic salinity. By contrast, some tailor from oceanic waters showed evidence of having spent considerable time in the bay, and some fish from the bay had oceanic signatures. This suggested that tailor were more migratory than snapper. The similarity in the distribution of the isotopic signatures (from oceanic to hypersaline) in otolith carbonate from tailor from oceanic waters north of Shark Bay (Koks Island), and from those within Shark Bay, indicated a single stock in this region (in contrast to pink snapper). Moreover, tailor from coastal south-western Australia and from the Shark Bay area could be considered seperately for some management purposes. For pink snapper stocks from oceanic waters, oxygen isotope signatures were clearly related to water temperature although the temperature relationship was obscured for fish within Shark Bay because of the strength of the signal generated by the hypersaline water. For tailor the temperature relationship was not obvious, probably because migrations of tailor smeared the temperature effect, and the hypersaline Shark Bay waters dominated, and, possibly, at the southern extemity of the range, the freshwater in some estuaries influenced the isotopic signatures of the otolith carbonate. Strontium/calcium ratios in pink snapper otoliths also indicated a separation of stocks, but for tailor overlap of signatures again suggested migratory behaviour.     

Ecological genomics of marine Roseobacters

Bacterioplankton of the marine Roseobacter clade have genomes that reflect a dynamic environment and diverse interactions with marine plankton. Comparative genome sequence analysis of three cultured representatives suggests that cellular requirements for nitrogen are largely provided by regenerated ammonium and organic compounds (polyamines, allophanate, and urea), while typical sources of carbon include amino acids, glyoxylate, and aromatic metabolites. An unexpectedly large number of genes are predicted to encode proteins involved in the production, degradation, and efflux of toxins and metabolites. A mechanism likely involved in cell-to-cell DNA or protein transfer was also discovered: vir-related genes encoding a type IV secretion system typical of bacterial pathogens. These suggest a potential for interacting with neighboring cells and impacting the routing of organic matter into the microbial loop. Genes shared among the three roseobacters and also common in nine draft Roseobacter genomes include those for carbon monoxide oxidation, dimethylsulfoniopropionate demethylation, and aromatic compound degradation. Genes shared with other cultured marine bacteria include those for utilizing sodium gradients, transport and metabolism of sulfate, and osmoregulation.     

Acetylene reduction byDaviesia mimosoides under Eucalyptus

Summary Daviesia mimosoides is a common understorey legume in Eucalyptus forests of the Brindabella Range in southeastern Australia, capable of fixing atmospheric nitrogen. Rates of N fixation were measured by the acetylene-reduction technique over a growing season in the field. Pot trials under controlled conditions were also carried out to elucidate effects of soil moisture, temperature, and light. Average rates in the field varied from about 1–5 μ mol C₂H₄/g/h (wet weight of nodule), but rates up to 14 μ mol C₂H₄/g/h were measured in optimum controlled conditions. Annual N-fixation rates approximate 4.5–7.0 kg/ha. In pot trials, rate of acetylene reduction decreased with soil moisture to about−10 MPa tension, with a marked depression at about−6 MPa, but within the normal field range of soil moisture there was little correlation of moisture with average acetylene reduction rate. Rates were similar in the temperature range of 20–30°C, but were depressed by either low or high temperature (<10 or >30°C). Diurnal fluctuations in acetylene reduction rates were not correlated with solar radiation, but rates were limited by high mid-day temperatures.