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Notes: Coupled thermal-mechanical models are used to investigate interactions between metamorphism, deformation and exhumation in large convergent orogens, and the implications of coupling and feedback between these processes for observed structural and metamorphic styles. The models involve subduction of suborogenic mantle lithosphere, large amounts of convergence (≥ 450 km) at 1 cm yr−1, and a slope-dependent erosion rate. The model crust is layered with respect to thermal and rheological properties — the upper crust (0–20 km) follows a wet quartzite flow law, with heat production of 2.0 μW m−3, and the lower crust (20–35 km) follows a modified dry diabase flow law, with heat production of 0.75 μW m−3. After 45 Myr, the model orogens develop crustal thicknesses of the order of 60 km, with lower crustal temperatures in excess of 700 °C. In some models, an additional increment of weakening is introduced so that the effective viscosity decreases to 1019 Pa.s at 700 °C in the upper crust and 900 °C in the lower crust. In these models, a narrow zone of outward channel flow develops at the base of the weak upper crustal layer where T≥600 °C. The channel flow zone is characterised by a reversal in velocity direction on the pro-side of the system, and is driven by a depth-dependent pressure gradient that is facilitated by the development of a temperature-dependent low viscosity horizon in the mid-crust. Different exhumation styles produce contrasting effects on models with channel flow zones. Post-convergent crustal extension leads to thinning in the orogenic core and a corresponding zone of shortening and thrust-related exhumation on the flanks. Velocities in the pro-side channel flow zone are enhanced but the channel itself is not exhumed. In contrast, exhumation resulting from erosion that is focused on the pro-side flank of the plateau leads to ‘ductile extrusion’ of the channel flow zone. The exhumed channel displays apparent normal-sense offset at its upper boundary, reverse-sense offset at its lower boundary, and an ‘inverted’ metamorphic sequence across the zone. The different styles of exhumation produce contrasting peak grade profiles across the model surfaces. However, P–T–t paths in both cases are loops where Pmax precedes Tmax, typical of regional metamorphism; individual paths are not diagnostic of either the thickening or the exhumation mechanism. Possible natural examples of the channel flow zones produced in these models include the Main Central Thrust zone of the Himalayas and the Muskoka domain of the western Grenville orogen.

Notes: Alterations of the axonal transport and microtubule network are potential causes of motor neurodegeneration in mice expressing a mutant form of the superoxide dismutase 1 (SOD1G37R) linked to amyotrophic lateral sclerosis (ALS). In the present study, we investigated the biology of microtubule-associated proteins (MAPs), responsible for the formation and stabilization of microtubules, in SOD1G37R mice. Our results show that the protein levels of MAP2, MAP1A, tau 100 kDa and tau 68 kDa species decrease significantly as early as 5 months before onset of symptoms in the spinal cord of SOD1G37R mice, whereas decrease in levels of tau 52–55 kDa species is most often noted with the manifestation of the clinical symptoms. Interestingly, there was no change in the protein levels of MAPs in the brain of SOD1G37R mice, a CNS organ spared by the mutant SOD1 toxicity. Remarkably, as early as 5 months before disease onset, the binding affinities of MAP1A, MAP2 and tau isoforms to the cytoskeleton decreased in spinal cord of SOD1G37R mice. This change correlated with a hyperphosphorylation of the soluble tau 52–55 kDa species at epitopes recognized by the antibodies AT8 and PHF-1. Finally, a shift in the distribution of MAP2 from the cytosol to the membrane is detected in SOD1G37R mice at the same stage. Thus, alterations in the integrity of microtubules are early events of the neurodegenerative processes in SOD1G37R mice.

Notes: Abstract: The carboxyl methylation of secretory proteins in vivo was investigated in bovine adrenal medullary cells in culture. Chromogranin A., the major intragranular secretory protein in adrenal medullary cells, and other secretory proteins were found to be carboxyl-methylated within secretory vesicles. The in vivo labeling pattern using [methyl-3H]methionine and the in vitro labeling pattern using S-adenosyl-[methyl-14C]methionine of intravesicular secretory proteins were similar. The detection of methylated chromogranin A in mature secretory vesicles required 3–6 h, a time consistent with the synthesis and storage of secretory proteins in this tissue. Carboxyl-methylated chromogranin A was secreted from medullary cells by exocytosis via activation of nicotinic cholinergic receptor and recovered still under the methylated form in the incubation medium. Since protein-carboxylmethylase is cytosolic, these results suggest that methylation of secretory proteins is a co-translational phenomenon.

Notes: This paper presents a comparative study on the role of operating conditions in osmotic distillation (OD) and direct contact membrane distillation (DCMD). Comparisons were made for lab scale OD and DCMD experiments on two types of PVDF hollow fibres under similar operating conditions for the concentration of glucose solutions from 30 to 60% (w/w) at temperatures as low as 25 to 45°C. Analysis of the results indicated that temperature was the most influencing factor for process improvement for both OD and DCMD. The flux in DCMD was improved by 3 to 4 times when feed temperature increased by 15 degrees, while this figure was nearly 3 times for OD when feed temperature increased by 20 degrees. The flow rates of the two streams played a more important role in maintaining the driving force, and consequently the flux rate, in DCMD rather than in OD. It was found that feed velocity had significant effect on DCMD performance, but insignificant in OD. Feed concentration, as the determining factor on water activity and viscosity, caused a more serious reduction of the flux rate in the high concentration range of 45-60% rather than in the dilute region of 30-40%. The effect was more significant in DCMD than in OD. The ratio of DCMD flux over that of OD ranged from 0.41 to 0.66 for PV375 when concentrating glucose solutions 30-40% w/w and from 0.35 to 0.69 for PV650 when concentrating high solid content ones. However, DCMD can overcome the disadvantages of OD being poor consumers' perception, (due to the use of brine solution being a chemical), the potential problem of corrosion by the brine and the cost of its reconcentration.

Notes: Objective To observe the longitudinal changes in growth, and associated Doppler measurements, of the fetal circulation in pregnancies with a normal outcome and those complicated by pre-eclampsia, birth of a small for gestational age baby, or a combination of these complications.Methods Two hundred and ninety-two women had serial ultrasound scans performed from the 24th week of pregnancy. Measurements obtained included: the abdominal circumference, umbilical artery pulsatility index, the middle cerebral artery pulsatility index and time-averaged velocity, and the thoracic aorta pulsatility index and time-averaged velocity. Outcome measures included the birth of a small for gestational age infant, pre-eclampsia or a combination of these complications.Results One hundred and sixty-seven pregnancies ended in the normal birth of an appropriately grown infant at term, while 105 had a complicated outcome. They were divided into three categories: pre-eclampsia only (i.e. with the birth of an appropriately grown fetus, n= 13); small for gestational age only with no evidence of pre-eclampsia, n= 55; and pre-eclampsia complicated by the birth of a small for gestational age infant, n = 37. The group with pre-eclampsia complicated by small for gestational age was closest in characteristics to true clinical intrauterine growth restriction. A reduction in the abdominal circumference mirrored a rise in the umbilical artery pulsatility index and preceded changes in the middle cerebral artery and thoracic aorta. The greatest degree of change in the fetal circulation was observed during the three weeks preceding delivery. Ratios of the values obtained from the fetal and umbilical circulation demonstrated the greatest deviation from normal.Conclusions A reduction in fetal growth velocity preceded changes observed in the fetal circulation. Ratios of the fetal Doppler parameters provided the clearest evidence of deterioration in the fetal condition. The information provided may be of use in the diagnosis and management of the growth-restricted fetus.

Notes: Candida albicans causes a wide spectrum of diseases, ranging from mucocutaneous infections like oral thrush to disseminated candidiasis. Screening for C. albicans genes expressed within infected hosts might advance understanding of candidal pathogenesis, but is impractical using existing techniques. In this study, we used an antibody-based strategy to identify C. albicans genes expressed during thrush. We adsorbed sera from HIV-infected patients with thrush against candidal cells grown in vitro and screened a C. albicans genomic expression library. We identified 10 genes encoding immunogenic antigens and used reverse transcription-polymerase chain reaction to verify that they were induced within thrush pseudomembranes recovered from a patient. The in vivo induced genes are involved in diverse functions, including regulation of yeast-hyphal morphogenesis, adhesion to host cells, nutrient uptake, phospholipid biosynthesis and amino acid catabolism. Four genes encode known virulence determinants (HWP1, CST20, CPP1 and RBF1). Another gene, LPD1, for which a role in candidal pathogenesis is unknown, encodes a protein homologous to a bacterial virulence determinant. Most importantly, disruption of CaNOT5, a newly identified gene, conferred defects in morphogenesis, decreased adherence to human buccal epithelial cells and attenuated mortality during murine disseminated candidiasis, proving that our strategy can identify genes encoding novel virulence determinants.