| 1. |
- Weber, Michael A, et al.
(author)
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A selective endothelin-receptor antagonist to reduce blood pressure in patients with treatment-resistant hypertension : a randomised, double-blind, placebo-controlled trial
- 2009
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In: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 374:9699, s. 1423-1431
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Journal article (peer-reviewed)abstract
- BackgroundHypertension cannot always be adequately controlled with available drugs. We investigated the blood-pressure-lowering effects of the new vasodilatory, selective endothelin type A antagonist, darusentan, in patients with treatment-resistant hypertension.MethodsThis randomised, double-blind study was undertaken in 117 sites in North and South America, Europe, New Zealand, and Australia. 379 patients with systolic blood pressure of 140 mm Hg or more (≥130 mm Hg if patient had diabetes or chronic kidney disease) who were receiving at least three blood-pressure-lowering drugs, including a diuretic, at full or maximum tolerated doses were randomly assigned to 14 weeks' treatment with placebo (n=132) or darusentan 50 mg (n=81), 100 mg (n=81), or 300 mg (n=85) taken once daily. Randomisation was made centrally via an automated telephone system, and patients and all investigators were masked to treatment assignments. The primary endpoints were changes in sitting systolic and diastolic blood pressures. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00330369.FindingsAll randomly assigned participants were analysed. The mean reductions in clinic systolic and diastolic blood pressures were 9/5 mm Hg (SD 14/8) with placebo, 17/10 mm Hg (15/9) with darusentan 50 mg, 18/10 mm Hg (16/9) with darusentan 100 mg, and 18/11 mm Hg (18/10) with darusentan 300 mg (p<0·0001 for all effects). The main adverse effects were related to fluid accumulation. Oedema or fluid retention occurred in 67 (27%) patients given darusentan compared with 19 (14%) given placebo. One patient in the placebo group died (sudden cardiac death), and five patients in the three darusentan dose groups combined had cardiac-related serious adverse events.InterpretationDarusentan provides additional reduction in blood pressure in patients who have not attained their treatment goals with three or more antihypertensive drugs. As with other vasodilatory drugs, fluid management with effective diuretic therapy might be needed.
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| 2. |
- Elsik, Christine G., et al.
(author)
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The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
- 2009
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
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Journal article (peer-reviewed)abstract
- To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
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| 3. |
- Richards, Stephen, et al.
(author)
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The genome of the model beetle and pest Tribolium castaneum.
- 2008
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In: Nature. - 1476-4687. ; 452:7190, s. 949-55
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Journal article (peer-reviewed)abstract
- Tribolium castaneum is a representative of earth’s most numerous eukaryotic order, a powerful model organism for the study of generalized insect development, and also an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved an ability to interact with a diverse chemical environment as evidenced by large expansions in odorant and gustatory receptors, as well as p450 and other detoxification enzymes. Developmental patterns in Tribolium are more representative of other arthropods than those found in Drosophila, a fact represented in gene content and function. For one, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, and some are expressed in the growth zone crucial for axial elongation in short germ development. Systemic RNAi in T. castaneum appears to use mechanisms distinct from those found in C. elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.
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| 4. |
- Yin, Henry H, et al.
(author)
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Ethanol reverses the direction of long-term synaptic plasticity in the dorsomedial striatum.
- 2007
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In: The European journal of neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 25:11, s. 3226-32
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Journal article (peer-reviewed)abstract
- The striatum is a critical structure for the control of voluntary behaviour, and striatal synaptic plasticity has been implicated in instrumental learning. As ethanol consumption can cause impairments in cognition, learning, and action selection, it is important to understand the effects of this drug on striatal function. In this study we examined the effects of ethanol on long-term synaptic plasticity in the dorsomedial striatum (DMS), a striatal subregion that plays a central role in the acquisition and selection of goal-directed actions. Ethanol was found to impair N-methyl-d-aspartic acid receptor (NMDAR)-dependent long-term potentiation (LTP) dose-dependently in the DMS, and to promote long-term depression (LTD) at the highest concentration (50 mm) used. These results suggest that ethanol, at a concentration usually associated with mild intoxication, could significantly change experience-dependent modification of corticostriatal circuits underlying the learning of goal-directed instrumental actions.
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