The VCAM-1 gene that encodes the vascular cell adhesion molecule is a target of the Sry-related high mobility group box gene, Sox18

VCAM-1 (vascular cell adhesion molecule-1) and Sox18 are involved in vascular development. VCAM-1 is an important adhesion molecule that is expressed on endothelial cells and has a critical role in endothelial activation, inflammation, lymphatic pathophysiology, and atherogenesis. The Sry-related high mobility group box factor Sox18 has previously been implicated in endothelial pathologies. Mutations in human and mouse Sox18 leads to hypotrichosis and lymphedema. Furthermore, both Sox18 and VCAM-1 have very similar spatio-temporal patterns of expression, which is suggestive of crosstalk. We use biochemical techniques, cell culture systems, and the ragged opossum (RaOP) mouse model with a naturally occurring mutation in Sox18 to demonstrate that VCAM-1 is an important target of Sox18. Transfection, site-specific mutagenesis, and gel shift analyses demonstrated that Sox18 directly targeted and trans-activated VCAM-1 expression. Importantly, the naturally occurring Sox18 mutant attenuates the expression and activation of VCAM-1 in vitro. Furthermore, in vivo quantitation of VCAM-1 mRNA levels in wild type and RaOP mice demonstrates that RaOP animals show a dramatic and significant reduction in VCAM-1 mRNA expression in lung, skin, and skeletal muscle. Our observation that the VCAM-1 gene is an important target of SOX18 provides the first molecular insights into the vascular abnormalities in the mouse mutant ragged and the human hypotrichosis-lymphedematelangiectasia disorder.

Linkage and Association Analysis of Radiation Damage Repair Genes XRCC3 and XRCC5 with Nevus Density in Adolescent Twins

Previous studies have shown that a deficiency in DNA damage repair is associated with increased cancer risk, and exposure to UV radiation is a major risk factor for the development of malignant melanoma. High density of common nevi (moles) is a major risk factor for cutaneous melanoma. A nevus may result from a mutation in a single UV-exposed melanocyte which failed to repair DNA damage in one or more critical genes. XRCC3 and XRCC5 may have an effect on nevus count through their function as components of DNA repair processes that may be involved directly or indirectly in the repair of DNA damage due to UV radiation. This study aims to test the hypothesis that the frequency of flat or raised moles is associated with polymorphism at or near these DNA repair genes, and that certain alleles are associated with less efficient DNA repair, and greater nevus density. Twins were recruited from schools in south eastern Queensland and were examined close to their 12th birthday. Nurses examined each individual and counted all moles on the entire body surface. A 10cM genome scan of 274 families (642 individuals) was performed and microsatellite polymorphisms in XRCC3 and adjacent to XRCC5 were also typed. Linkage and association of nevus count to these loci were tested simultaneously using a structural-equation modeling approach implemented in MX. There is weak evidence for linkage of XRCC5 to a QTL influencing raised mole count, and also weak association. There is also weak evidence for association between flat mole count and XRCC3. No tests were significant after correction for testing multiple alleles, nor were any of the tests for total association significant. If variation in XRCC3 or XRCC5 influences UV sensitivity, and indirectly affects nevus density, then the effects are small.

High frequency of BRAF mutations in nevi

To evaluate the timing of mutations in BRAF (v-raf murine sarcoma viral oncogene homolog B1) during melanocytic neoplasia, we carried out mutation analysis on microdissected melanoma and nevi samples. We observed mutations resulting in the V599E amino-acid substitution in 41 of 60 (68%) melanoma metastases, 4 of 5 (80%) primary melanomas and, unexpectedly, in 63 of 77 (82%) nevi. These data suggest that mutational activation of the RAS/RAF/MAPK pathway in nevi is a critical step in the initiation of melanocytic neoplasia but alone is insufficient for melanoma tumorigenesis.

ADH genotype does not modify the effects of alcohol on high-density lipoprotein

Background: Alcohol consumption has beneficial effects on mortality which are mainly due to reduction in cardiovascular disease. These are believed to be due, at least in part, to the increase in plasma high-density lipoprotein (HDL) which is associated with alcohol consumption. It has been proposed that ADH3 genotype modifies the relationships between alcohol intake and cardiovascular disease by altering the HDL response to alcohol. The aim of this paper was to test for effects of ADH2 and ADH3 genotypes on the response of HDL components to habitual alcohol consumption. Methods: Adult male and female subjects were genotyped for ADH2 and ADH3; and plasma HDL cholesterol, apolipoprotein A-I, and apolipoprotein A-II were measured. Nine hundred one subjects had both ADH2 and ADH3 genotypes and HDL cholesterol results, while 753 had both genotypes and all three lipid results. The effect of alcohol intake on the three measured HDL components, and a factor score derived from them, was estimated for each of the ADH2 and ADH3 genotype groups. Results: All the measured components of HDL increased with increasing alcohol consumption over the range of intakes studied, 0-4 drinks per day. There were no significant interactions between alcohol consumption and ADH2 or ADH3 genotypes. Conclusions: The concept that alcohol dehydrogenase genotype and alcohol metabolic rate modify the effects of alcohol on plasma HDL concentration is not supported by our results.

Exceptionally high-rate nitrification in sequencing batch reactors treating high ammonia landfill leachate

The nitrogen removal capacity of a suspended culture system treating mature landfill leachate was investigated. Leachate containing high ammonium levels of 300-900 mg N/L was nitrified in a bench scale sequencing batch reactor. Leachate from four different landfills was treated over a two year period for the removal of nitrogen. In this time, a highly specific nitrifying culture was attained that delivered exceptionally high rates of ammonia removal. No sludge was wasted from the system to increase the throughput and up to 13 g/L of MLSS was obtained. Settleability of the purely nitrifying biomass was excellent with SVI less than 40 mL/g, even at the high sludge concentrations. Nitrification rates up to 246 mg NI(L h) (5.91 g N/(L d)) and specific nitrification rates of 36 mg N/(gVSS h) (880 mg N/(gVSS d)) were obtained. The loading to the system at this time allowed complete nitrification of the leachate with a hydraulic retention time of only 5 hours. Following these successful treatability studies, a full-scale plant was designed and built at one of the landfills investigated.

Low input tillage/cropping systems for limited resource areas

Agriculture in limited resource areas is characterized by small farms which an generally too small to adequately support the needs of an average farm family. The farming operation can be described as a low input cropping system with the main energy source being manual labor, draught animals and in some areas hand tractors. These farming systems are the most important contributor to the national economy of many developing countries. The role of tillage is similar in dryland agricultural systems in both the high input (HICS) and low input cropping systems (LICS), however, wet cultivation or puddling is unique to lowland rice-based systems in low input cropping systems. Evidence suggest that tillage may result in marginal increases in crop yield in the short term, however, in the longer term it may be neutral or give rise to yield decreases associated with soil structural degradation. On marginal soils, tillage may be required to prepare suitable seedbeds or to release adequate Nitrogen through mineralization, but in the longer term, however, tillage reduces soil organic matter content, increases soil erodibility and the emission of greenhouse gases. Tillage in low input cropping systems involves a very large proportion of the population and any changes: in current practices such as increased mechanization will have a large social impact such as increased unemployment and increasing feminization of poverty, as mechanization may actually reduce jobs for women. Rapid mechanization is likely to result in failures, but slower change, accompanied by measures to provide alternative rural employment, might be beneficial. Agriculture in limited resource areas must produce the food and fiber needs of their community, and its future depends on the development of sustainable tillage/cropping systems that are suitable for the soil and climatic conditions. These should be based on sound biophysical principles and meet the needs of and he acceptable to the farming communities. Some of the principle requirements for a sustainable system includes the maintenance of soil health, an increase in the rain water use efficiency of the system, increased use of fertilizer and the prevention of erosion. The maintenance of crop residues on the surface is paramount for meeting these requirements, and the competing use of crop residues must be met from other sources. These requirements can be met within a zonal tillage system combined with suitable agroforestry, which will reduce the need for crop residues. It is, however, essential that farmers participate in the development of any new technologies to ensure adoption of the new system. (C) 2001 Elsevier Science B.V. All rights reserved.

Calculation of electric fields induced by body and head motion in high-field MRI

In modern magnetic resonance imaging (MRI), patients are exposed to strong, nonuniform static magnetic fields outside the central imaging region, in which the movement of the body may be able to induce electric currents in tissues which could be possibly harmful. This paper presents theoretical investigations into the spatial distribution of induced electric fields and currents in the patient when moving into the MRI scanner and also for head motion at various positions in the magnet. The numerical calculations are based on an efficient, quasi-static, finite-difference scheme and an anatomically realistic, full-body, male model. 3D field profiles from an actively shielded 4T magnet system are used and the body model projected through the field profile with a range of velocities. The simulation shows that it possible to induce electric fields/currents near the level of physiological significance under some circumstances and provides insight into the spatial characteristics of the induced fields. The results are extrapolated to very high field strengths and tabulated data shows the expected induced currents and fields with both movement velocity and field strength. (C) 2003 Elsevier Science (USA). All rights reserved.

Optimising high-intensity treadmill training using the running speed at maximal O-2 uptake and the time for which this can be maintained

The aim of this study was to compare the effects of two high-intensity, treadmill interval-training programs on 3000-m and 5000-m running performance. Maximal oxygen uptake ((V) over dot O-2max), the running speed associated with (V) over dot O-2max (nu (V) over dot O-2max), the time for which nu (V) over dot O-2max can be maintained (T-max), running economy (RE), ventilatory threshold (VT) and 3000-m and 5000-m running times were determined in 27 well-trained runners. Subjects were then randomly assigned to three groups; (1) 60% T-max (2) 70% T-max and (3) control. Subjects in the control group continued their normal training and subjects in the two T-max groups undertook a 4-week treadmill interval-training program with the intensity set at nu (V) over dot O-2max and the interval duration at the assigned T-max. These subjects completed two interval-training sessions per week (60% T-max = six intervals/session, 70% T-max group = five intervals/session). Subjects were re-tested on all parameters at the completion of the training program. There was a significant improvement between pre- and post-training values in 3000-m time trial (TT) performance in the 60% T-max group compared to the 70% T,,a, and control groups [mean (SE); 60% T-max = 17.6 (3.5) s, 70% T-max = 6.3 (4.2) s, control = 0.5 (7.7) s]. There was no significant effect of the training program on 5000-m TT performance [60% T-max = 25.8 (13.8) s, 70% T-max = 3.7 (11.6) s, control = 9.9 (13.1) s]. Although there were no significant improvements in (V) over dot O-2max, nu (V) over dot (2max) and RE between groups, changes in (V) over dot O-2max and RE were significantly correlated with the improvement in the 3000-m TT. Furthermore, VT and T-max were significantly higher in the 60% Tmax group post-compared to pre-training. In conclusion, 3000-m running performance can be significantly improved in a group of well-trained runners, using a 4-week treadmill interval training program at nu (V) over dot O-2max with interval durations of 60% T-max.

Physiological responses to repeated bouts of high-intensity ultraendurance cycling - a field study case report

The present study aimed to 1) examine the relationship between laboratory-based measures and high-intensity ultraendurance (HIU) performance during an intermittent 24-h relay ultraendurance mountain bike race (similar to20 min cycling, similar to60min recovery), and 2) examine physiological and performance based changes throughout the HIU event. Prior to the HIU event, four highly-trained male cyclists (age = 24.0 +/- 2.1 yr; mass = 75.0 +/- 2.7 kg; (V)over dot O-2peak = 70 +/- 3 ml.kg(-1).min(-1)) performed 1) a progressive exercise test to determine peak Volume of oxygen uptake ((V)over dot O-2peak), peak power output (PPO), and ventilatory threshold (T-vent), 2) time-to-fatigue tests at 100% (TF100) and 150% of PPO (TF150), and 3) a laboratory simulated 40-km time trial (TT40). Blood lactate (Lac(-)), haematocrit and haemoglobin were measured at 6-h intervals throughout the HIU event, while heart rate (HR) was recorded continuously. Intermittent HIU performance, performance HR, recovery HR, and Lac declined (P < 0.05), while plasma volume expanded (P < 0.05) during the HIU event. TF100 was related to the decline in lap time (r = -0.96; P < 0.05), and a trend (P = 0.081) was found between TF150 and average intermittent HIU speed (r = 0.92). However, other measures (V)over dot O-2peak, PPO, T-vent, and TT40) were not related to HIU performance. Measures of high-intensity endurance performance (TF100, TF150) were better predictors of intermittent HIU performance than traditional laboratory-based measures of aerobic capacity.

High rate of detection of primary aldosteronism, including surgically treatable forms, after 'non-selective' screening of hypertensive patients

Background Wide testing of the aldosterone: renin ratio among hypertensive individuals has revealed primary aldosteronism to be common, with most patients normokalaemic. Some investigators, however, have reported aldosterone-producing adenoma to be rare among patients so detected. Objective To test the hypothesis that differences among reported studies in the rate of detection of aldosterone-producing adenoma (as opposed to bilateral adrenal hyperplasia) reflect differences in the procedures used for diagnosis of primary aldosteronism, and the methods used to identify aldosterone-producing adenomas. Methods In the newly established Princess Alexandra Hospital Hypertension Unit (PAHHU), we used procedures developed by Greenslopes Hospital Hypertension Unit (which reports that more than 30% of patients with primary aldosteronism have aldosterone-producing adenomas) to diagnose primary aldosteronism and determine the subtype. All patients with an increased aldosterone: renin ratio (measured after correction for hypokalaemia and while the patient was not receiving interfering medications) underwent fludrocortisone suppression testing to confirm or exclude primary aldosteronism; if they were positive, they underwent genetic testing to exclude glucocorticoid-remediable aldosteronism before adrenal venous sampling was used to differentiate lateralizing from bilateral primary aldosteronism. Results This approach allowed PAHHU to diagnose, within 2 years, 54 patients [only seven (13%) hypokalaemic] with primary aldosteronism. All tested negative for glucocorticoid-remediable aldosteronism. Aldosterone production was lateralized to one adrenal in 15 patients (31%; only six hypokalaemic) and was bilateral in 34 (69%; all normokalaemic) of 49 patients who underwent adrenal venous sampling. Among patients with lateralizing adrenal hyperplasia, computed tomography revealed an ipsilateral mass in only six and a contralateral lesion in one. Fourteen patients underwent unilateral adrenalectomy, which cured the hypertension in seven and improved it in the remainder. In patients with bilateral primary aldlosteronism, hypertension responded to spironolactone (112.5-50 mg/ day) or amiloride (2.5-10 mg/day). Conclusion When performed with careful regard to confounding factors, measurement of the aldosterone: renin ratio in all hypertensive individuals, followed by fludrocortisone suppression testing to confirm or exclude primary aldosteronism and adrenal venous sampling to determine the subtype, can result in the detection of significant numbers of patients with specifically treatable or potentially curable hypertension. (C) 2003 Lippincott Williams Wilkins.

Nitrification of high strength ammonia wastewtaer treatment - process selection is the major factor.

Biological nitrogen removal via the nitrite pathway in wastewater treatment is very important in Saving the cost of aeration and as an electron donor for denitrification. Wastewater nitrification and nitrite accumulation were carried out in a biofilm airlift reactor with autotrophic nitrifying biofilm. The biofilm reactor showed almost complete nitrification and most of the oxidized ammonium was present as nitrite at the ammonium load of 1.5 to 3.5 kg N/m3.d. Nitrite accumulation was stably achieved by the selective inhibition of nitrite oxidizers with free ammonia and dissolved oxygen limitation. Stable 100% conversion to nitrite could also be achieved even under the absence of free ammonia inhibition on nitrite oxidizers. Batch ammonium oxidation and nitrite oxidation with nitrite accumulating nitrifying biofilm showed that nitrite Oxidation was completely inhibited when free ammonia is higher than 0.2 mg N/L. However, nitrite oxidation activity was recovered as soon as the free ammonia concentration was below the threshold level when dissolved oxygen concentration was not the limiting factor. Fluorescence in situ hybridization analysis of cryosectioned nitrite accumulating nitrifying biofilm showed that the β-subclass of Proteobacteria, where ammonia oxidizers belong, was distributed outside the biofilm whereas the α-subclass of Proteobacteria, where nitrite oxidizers belong, was found mainly in the inner part of the biofilm. It is likely that dissolved oxygen deficiency or limitation in the inner part of the nitrifying biofilm, where nitrite oxidizers exist, is responsible for the complete shut down of the nitrite oxidizers activity under the absence of free ammonia inhibition.