G-protein beta3 subunit gene (GNB3) variant in causation of essential hypertension

-Essential hypertensives display enhanced signal transduction through pertussis toxin-sensitive G proteins. The T allele of a C825T variant in exon 10 of the G protein beta3 subunit gene (GNB3) induces formation of a splice variant (Gbeta3-s) with enhanced activity. The T allele of GNB3 was shown recently to be associated with hypertension in unselected German patients (frequency=0.31 versus 0.25 in control). To confirm and extend this finding in a different setting, we performed an association study in Australian white hypertensives. This involved an extensively examined cohort of 110 hypertensives, each of whom were the offspring of 2 hypertensive parents, and 189 normotensives whose parents were both normotensive beyond age 50 years. Genotyping was performed by polymerase chain reaction and digestion with BseDI, which either cut (C allele) or did not cut (T allele) the 268-bp polymerase chain reaction product. T allele frequency in the hypertensive group was 0.43 compared with 0.25 in the normotensive group (chi2=22; P=0.00002; odds ratio=2.3; 95% CI=1.7 to 3.3). The T allele tracked with higher pretreatment blood pressure: diastolic=105+/-7, 109+/-16, and 128+/-28 mm Hg (mean+/-SD) for CC, CT, and TT, respectively (P=0.001 by 1-way ANOVA). Blood pressures were higher in female hypertensives with a T allele (P=0.006 for systolic and 0.0003 for diastolic by ANOVA) than they were in male hypertensives. In conclusion, the present study of a group with strong family history supports a role for a genetically determined, physiologically active splice variant of the G protein beta3 subunit gene in the causation of essential hypertension.

Resonance de-enhancement in the 2(1)A(g) state of trans-azobenzene

We analyze the origin of de-enhancement for a number of vibrational modes in the 2(1)A(g) excited state of trans-azobenzene. We have used the time-dependent wave packet analysis of the RR intensities by including the multimode damping effects in the calculation. This avoids the use of unrealistically large values for the damping parameter. It is concluded that the de-enhancement is caused by the interference between the two uncoupled electronic states, and that the intensities observed under the so-called symmetry forbidden 2(1)A(g) <-- 1(1)A(g) transition are purely due to resonance excitation. It is also observed that the use of the time-dependent approach to study the de-enhancement effects caused by multiple electronic states on the RR intensities is not necessarily useful if one is interested in the structural dynamics.

G-jitter effects on half floating-zone convection in intermediate-frequency range

The g-jitter influence on thermocapillary convection and critical Marangoni number in a liquid bridge of half-floating rone was discussed in the low frequency range of 0.4 to 1.5 Hz in a previous paper. This paper extended the experiments to the intermediate frequency range of 2 to 18 Hz, which htrs often been recorded as vibration environment of spacecrafts. The experiment was completed on the deck of a vibration machine, which gave a periodical applied acceleration to simulate the effects of g-jitter. The experimental results in the intermediate frequency range are different from that in the low frequency range. The velocity field and the shape of the free surface have periodical fluctuations in response to g-jitter. The amplitude of the periodical varying part of the temperature response decreases obviously with increasing frequency of g-jitter and vanishes almost when the frequency of g-jitter is high enough. The critical Marangoni number is defined to describe the transition from a periodical convection in response to g-jitter to an oscillatory convection due to internal instability, and will increase with increasing g-jitter frequency. According to the spectral analysis, it can be found that the oscillatory part of temperature is a superposition of two harmonic waves if the Marangoni number is larger than a critical value.

Survey of sediment quality in Sabine Lake, Texas and vicinity

The toxicity of sediments in Sabine Lake, Texas, and adjoining Intracoastal Waterway canals was determined as part of bioeffects assessment studies managed by NOAA’s National Status and Trends Program. The objectives of the survey were to determine: (1) the incidence and degree of toxicity of sediments throughout the study area; (2) the spatial patterns (or gradients) in chemical contamination and toxicity, if any, throughout the study area; (3) the spatial extent of chemical contamination and toxicity; and (4) the statistical relationships between measures of toxicity and concentrations of chemicals in the sediments. Surficial sediment samples were collected during August, 1995 from 66 randomly-chosen locations. Laboratory toxicity tests were performed as indicators of potential ecotoxicological effects in sediments. A battery of tests was performed to generate information from different phases (components) of the sediments. Tests were selected to represent a range in toxicological endpoints from acute to chronic sublethal responses. Toxicological tests were conducted to measure: reduced survival of adult amphipods exposed to solid-phase sediments; impaired fertilization success and abnormal morphological development in gametes and embryos, respectively, of sea urchins exposed to pore waters; reduced metabolic activity of a marine bioluminescent bacteria exposed to organic solvent extracts; and induction of a cytochrome P-450 reporter gene system in exposures to solvent extracts of the sediments. Chemical analyses were performed on portions of each sample to quantify the concentrations of trace metals, polynuclear aromatic hydrocarbons, and chlorinated organic compounds. Correlation analyses were conducted to determine the relationships between measures of toxicity and concentrations of potentially toxic substances in the samples. Based upon the compilation of results from chemical analyses and toxicity tests, the quality of sediments in Sabine Lake and vicinity did not appear to be severely degraded. Chemical concentrations rarely exceeded effects-based numerical guidelines, suggesting that toxicant-induced effects would not be expected in most areas. None of the samples was highly toxic in acute amphipod survival tests and a minority (23%) of samples were highly toxic in sublethal urchin fertilization tests. Although toxic responses occurred frequently (94% of samples) in urchin embryo development tests performed with 100% pore waters, toxicity diminished markedly in tests done with diluted pore waters. Microbial bioluminescent activity was not reduced to a great degree (no EC50 <0.06 mg/ml) and cytochrome P-450 activity was not highly induced (6 samples exceeded 37.1 ug/g benzo[a]pyrene equivalents) in tests done with organic solvent extracts. Urchin embryological development was highly correlated with concentrations of ammonia and many trace metals. Cytochrome P450 induction was highly correlated with concentrations of a number of classes of organic compounds (including the polynuclear aromatic hydrocarbons and chlorinated compounds). (PDF contains 51 pages)

Impact assessment of Niger State fisheries legislation on fisheries conservation in Edozhigi local government area (L.G.A.) of Niger State

A preliminary survey was conducted among the fishermen in five selected villages in Edozhigi L.G.A. of Niger State. One hundred and fifty fishermen were randomly selected and interviewed to find out the impact of Niger State fisheries legislation on fisheries conservation resources in the area. The analysis of data collected using descriptive statistics indicated that undersized mesh of gill nets, beach seines and traps are being used unabated. Also, fenced barriers across the entrance of flood plain ponds and Ex-bow lakes from the main stream are in the area. The fisheries rules and regulations implementers are rarely seen or not seen at all in the area. The decreasing nature of fish catches was detected. It is observed that government policy on fish conversation is neglected due to inadequate or lack of funding for meaningful extension and implementation of the fisheries rules and regulations

Report on Fourth FIDAWOG Workshop held in Kisumo, 16 to 20 August 1999: summary of proceedings

The FIDAWOG workshop held at the Tom Mboya Labour College in Kisumu was the fourth stock assessment workshop held under the LVFRP programme. There were two main objectives: training in paper and report writing and presentation, and presentation of research results collected to date.

G protein signaling and vein graft intimal hyperplasia: reduction of intimal hyperplasia in vein grafts by a Gbetagamma inhibitor suggests a major role of G protein signaling in lesion development.

Vein grafting results in the development of intimal hyperplasia with accompanying changes in guanine nucleotide-binding (G) protein expression and function. Several serum mitogens that act through G protein-coupled receptors, such as lysophosphatidic acid, stimulate proliferative pathways that are dependent on the G protein betagamma subunit (Gbetagamma)-mediated activation of p21ras. This study examines the role of Gbetagamma signaling in intimal hyperplasia by targeting a gene encoding a specific Gbetagamma inhibitor in an experimental rabbit vein graft model. This inhibitor, the carboxyl terminus of the beta-adrenergic receptor kinase (betaARK(CT)), contains a Gbetagamma-binding domain. Vein graft intimal hyperplasia was significantly reduced by 37% (P<0.01), and physiological studies demonstrated that the normal alterations in G protein coupling phenotypically seen in this model were blocked by betaARK(CT) treatment. Thus, it appears that Gbetagamma-mediated pathways play a major role in intimal hyperplasia and that targeting inhibitors of Gbetagamma signaling offers novel intraoperative therapeutic modalities to inhibit the development of vein graft intimal hyperplasia and subsequent vein graft failure.

Myeloperoxidase G-463A polymorphism and Alzheimer's disease in the ApoEurope study

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Epidemiological and molecular genetic studies have shown the existence of several genes associated with increased risk of AD, the major genetic susceptibility locus coding for apolipoprotein E (apoE). A polymorphism in the myeloperoxidase gene (MPO) has previously been associated with AD susceptibility. However, results in the literature are controversial and seem to be dependent on several factors such as gender, apoE polymorphism or the genetic structure of the population. We investigated MPO G-463A and apoE polymorphism in 265 cases and 246 controls from the ApoEurope Study. In females, we found a significant association between MPO genotype and AD (P=0.034), GG genotype frequency being lower in cases (52.4%) as compared to controls (64.2%). In men, there was no significant effect of MPO polymorphism. No interaction was found between MPO polymorphism and apoE epsilon 4 allele. In conclusion, the G-463A polymorphism of MPO was statistically associated with AD in a gender-specific manner. However, given the low significance of P value we suggest no causal effect of the MPO gene in AD, as also evidenced in a recent meta-analysis. Our results support the hypothesis of a possible linkage disequilibrium between the MPO G-463A gene polymorphism and another functional variant involved in AD.

Poor relief in the north of Ireland 1850-1921

This examines the way in which poor relief, and in particular the Poor Law, operated in the north of Ireland from the end of the Great Famine through to Partition. Drawing on a range of primary sources it develops a picture of relief patterns, exploring the ways in which the poor law was administered and the ways in which the poor utilised the limited relief options available to them. The chapter provides an analysis of how releif patterns in the north reacted to broader social and political change, developed over time and compared to other regions within Ireland.

Missing Links, Cultural Modernity and the Dead: Anatomically Modern Humans in the Great Cave of Niah (Sarawak, Borneo)

The Great Cave of Niah in Sarawak (northern Borneo) came into the gaze of Western Science through the work of Alfred Russell Wallace, who came to Sarawak in the 1850s to search for ‘missing links’ in his pioneering studies of evolution and the natural history of Island Southeast Asia and Australasia. The work of Tom and Barbara Harrisson in the 1950s and 1960s placed the Great Cave, and particularly their key find, the ‘Deep Skull’, at the nexus of the evolving archaeological framework for the region: for decades the skull, dated in 1958 by adjacent charcoal to c.40,000 BP, was the oldest fossil of an anatomically modern human anywhere in the world and thus critical to ideas about human evolution and dispersal. Although several authorities later questioned the provenance and antiquity of the Deep Skull, renewed investigations of the Harrisson excavations since 2000 have shown that it can be attributed securely to a specific location in the Pleistocene stratigraphy, with direct U-series dating on a piece of the skull indicating an age for it of c.37,500 BP and the first evidence for associated human activity at the site going back to c.50,000 BP. The new work also indicates that the skull is part of a cultural deposit, perhaps a precursor to the long tradition in Borneo of processing of the dead and secondary burial. These indicators of cultural complexity chime with the complexity of the subsistence behaviour of the early users of the caves discussed by Philip Piper and Ryan Rabett in chapter ten of this volume.

The cyclin D1 (CCND1) rs9344 G&gt;A polymorphism predicts clinical outcome in colon cancer patients treated with adjuvant 5-FU-based chemotherapy

Recent evidence indicates a potential prognostic and predictive value for germline polymorphisms in genes involved in cell cycle control. We investigated the effect of cyclin D1 (CCND1) rs9344 G&gt;A in stage II/III colon cancer patients and validated the findings in an independent study cohort. For evaluation and validation set, a total of 264 and 234 patients were included. Patients treated with 5-fluorouracil-based chemotherapy, carrying the CCND1 rs9344 A/A genotype had significantly decreased time-to-tumor recurrence (TTR) in univariate analysis and multivariate analysis (hazard ratio (HR) 2.47; 95% confidence interval (CI) 1.16-5.29; P=0.019). There was no significant association between CCND1 rs9344 G&gt;A and TTR in patients with curative surgery alone. In the validation set, the A allele of CCND1 rs9344 G&gt;A remained significantly associated with decreased TTR in univariate and multivariate analyses (HR 1.94; 95% CI 1.05-3.58; P=0.035). CCND1 rs9344 G&gt;A may be a predictive and/or prognostic biomarker in stage II/III colon cancer patients, however, prospective trials are warranted to confirm our findings.

Effect of replacing grass silage with maize silage in the diet on bovine milk fatty acid composition

Even though extensive research has examined the role of nutrition on milk fat composition, there is less information on the impact of forages on milk fatty acid (FA) composition. In the current study, the effect of replacing grass silage (GS) with maize silage (MS) as part of a total mixed ration on animal performance and milk FA composition was examined using eight multiparous mid-lactation cows in a replicated 4 X 4 Latin square with 28-day experimental periods. Four treatments comprised the stepwise replacement of GS with MS (0, 160, 334 and 500 g/kg dry matter (DM)) in diets containing a 54:46 forage: concentrate ratio on a DM basis. Replacing GS with MS increased (P < 0.001) the DM intake, milk yield and milk protein content. Incremental replacement of GS with MS in the diet enhanced linearly (P < 0.001) the proportions of 6:0-14:0, decreased (P < 0.01) the 16:0 concentrations, but had no effect on the total milk fat saturated fatty acid content. Inclusion of MS altered the distribution of trans-18:1 isomers and enhanced (P < 0.05) total trans monounsaturated fatty acid and total conjugated linoleic acid content. Milk total n-3 polyunsaturated fatty acid (PUFA) content decreased with higher amounts of MS in the diet and n-6 PUFA concentration increased, leading to an elevated n-6: n-3 PUFA ratio. Despite some beneficial changes associated with the replacement of GS with MS, the overall effects on milk FA composition would not be expected to substantially improve long-term human health. However the role of forages on milk fat composition must also be balanced against the increases in total milk and protein yield on diets containing higher proportions of MS.

DNA variation in a 13-Mb region including the F9 gene: inferring the genealogical history and causal role of a hemophilia B mutation (IVS 5+13 A -> G)

About 5.5% of all UK hemophilia B patients have the base substitution IVS 5+13 A-->G as the only change in their factor (F)IX gene (F9). This generates a novel donor splice site which fits the consensus better than the normal intron 5 donor splice. Use of the novel splice site should result in a missense mutation followed by the abnormal addition of four amino acids to the patients' FIX. In order to explain the prevalence of this mutation, its genealogical history is examined. Analysis of restriction fragment length polymorphism in the 21 reference UK individuals (from different families) with the above mutation showed identical haplotypes in 19 while two differed from the rest and from each other. In order to investigate the history of the mutation and to verify that it had occurred independently more than once, the sequence variation in 1.5-kb segments scattered over a 13-Mb region including F9 was examined in 18 patients and 15 controls. This variation was then analyzed with a recently developed Bayesian approach that reconstructs the genealogy of the gene investigated while providing evidence of independent mutations that contribute disconnected branches to the genealogical tree. The method also provides minimum estimates of the age of the mutation inherited by the members of coherent trees. This revealed that 17 or 18 mutant genes descend from a founder who probably lived 450 years ago, while one patient carries an independent mutation. The independent recurrence of the IVS5+13 A-->G mutation strongly supports the conclusion that it is the cause of these patients' mild hemophilia.