1,024 research outputs found

    Evidence of synergistic/additive effects of sildenafil and erythropoietin in enhancing survival and migration of hypoxic endothelial cells

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    Endothelial cell dysfunction is a common event to several pathologies including pulmonary hypertension (PH), which is often associated with hypoxia. As the endothelium plays an essential role in regulating the dynamic interaction between pulmonary vasodilatation and vasoconstriction, this cell type is fundamental in the development of vascular remodelling and increased vascular resistance. We investigated the protective effects of sildenafil, a phosphodiesterase type 5 inhibitor, given in combination with erythropoietin (Epo) as it has been demonstrated that both drugs have anti-apoptotic effects on several cell types. Specifically, we examined the viability and angiogenetic properties of rat pulmonary artery endothelial cells upon exposure to either 21% or 1% oxygen, in presence of sildenafil (1 and 100 nM) and Epo (5 and 20 U/ml) alone or in combination (1 nM and 20 U/ml). Cell proliferation and viability were analysed by trypan blue staining, MTT assay and annexin V/PI stainings. In all assays the ability of the combination treatment in improving cell viability was superior to that of either drug alone. The angiogenetic properties were studied using a migration and a 3D collagen assay and the results revealed increases in the migration potential of endothelial cells as well as the ability to form tube-like structures in response to sildenafil and the combination treatment. We therefore conclude that both drugs exert protective effects on endothelial cells upon hypoxia, and that sildenafil enhances the migratory and angiogenetic properties, especially in hypoxic conditions. Furthermore, we present evidence of possible additive or synergistic effects of both drugs

    The Role of Colour in Categorial Judgements

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    Two experiments are reported that extend the findings of Ostergaard and Davidoff (1985) on the role of colour in object processing. Two types of categorial judgements were investigated from pictorial stimuli: size judgement and living/non-living classifications. The effect of real size on size judgements (Paivio, 1975) was replicated. It was found that colour did not affect either of the categorial judgements, but the facilitation occurring in object naming tasks was confirmed. It is argued that semantic judgements can precede name retrieval, that physical colour input does not enter the semantic system, and that the representation of object colour information in the semantic system may be largely verbal. </jats:p

    The power of model-to-crop translation illustrated by reducing seed loss from pod shatter in oilseed rape

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    Key message: Elucidation of key regulators in Arabidopsis fruit patterning has facilitated knowledge-translation into crop species to address yield loss caused by premature seed dispersal (pod shatter). Abstract: In the 1980s, plant scientists descended on a small weed Arabidopsis thaliana (thale cress) and developed it into a powerful model system to study plant biology. The massive advances in genetics and genomics since then have allowed us to obtain incredibly detailed knowledge on specific biological processes of Arabidopsis growth and development, its genome sequence and the function of many of the individual genes. This wealth of information provides immense potential for translation into crops to improve their performance and address issues of global importance such as food security. Here, we describe how fundamental insight into the genetic mechanism by which seed dispersal occurs in members of the Brassicaceae family can be exploited to reduce seed loss in oilseed rape (Brassica napus). We demonstrate that by exploiting data on gene function in model species, it is possible to adjust the pod-opening process in oilseed rape, thereby significantly increasing yield. Specifically, we identified mutations in multiple paralogues of the INDEHISCENT and GA4 genes in B. napus and have overcome genetic redundancy by combining mutant alleles. Finally, we present novel software for the analysis of pod shatter data that is applicable to any crop for which seed dispersal is a serious problem. These findings highlight the tremendous potential of fundamental research in guiding strategies for crop improvement

    Mesial temporal, diencephalic, and striatal contributions to deficits in single word reading, word priming, and recognition memory

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    Fifty-three volunteer participants were studied with the fade-in task (Ostergaard, 1998) to measure naming latency, word priming, and recognition-memory performance. and with morphometric magnetic resonance imaging (MRI) techniques to measure volumes of mesial temporal lobe, diencephalic, striatal, and neocortical structures. The relationship between measures of cerebral volume loss and performance deficits was modeled using simultaneous regression analyses in which the behavioral measures were dependent variables. The results suggested that damage in both hippocampal and amygdala/entorhinal areas as well as damage in the diencephalon and the nucleus accumbens all contributed independently to the severity of recognition-memory deficits. Both caudate nucleus damage and hippocampal damage contributed independently to increased naming latency (slowed single-word reading). Finally, only damage in the hippocampus appeared to result in decreased word priming. These results provide further evidence against the assertion that word priming represents a form of memory unaffected by damage to the mesial temporal lobes

    Brain Activation during Word Identification and Word Recognition

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    Previous memory research has suggested that the effects of prior study observed in priming tasks are functionally, and neurobiologically, distinct phenomena from the kind of memory expressed in conventional (explicit) memory tests. Evidence for this position comes from observed dissociations between memory scores obtained with the two kinds of tasks. However, there is continuing controversy about the meaning of these dissociations. In recent studies, Ostergaard (1998a, Memory Cognit, 26:40-60; 1998b, J. Int. Neuropsychol. Soc., in press) showed that simply degrading visual word stimuli can dramatically alter the degree to which word priming shows a dissociation from word recognition; i.e., effects of a number of factors on priming paralleled their effects on recognition memory tests when the words were degraded at test. In the present study, cerebral blood flow changes were measured while subjects performed the word identification (reading) and recognition memory tasks used previously by Ostergaard. The results are the direct comparisons of the two tasks and the effects of stimulus degradation on blood flow patterns during the tasks. Clear differences between word identification and word recognition were observed: the latter task evoked considerably more prefrontal activity and stronger cerebellar activation. Stimulus degradation was associated with focal increases in bilateral fusiform regions within the occipital lobe. No task, degradation, or item repetition effects were demonstrated in mesial temporal regions, no repetition effects were observed in any region, and there was no evidence for different effects of stimulus degradation in the priming and recognition memory conditions. Power limitations may have contributed to the null effects

    Rapid identification of mutations in GJC2 in primary lymphoedema using whole exome sequencing combined with linkage analysis with delineation of the phenotype.

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    Background: Primary lymphoedema describes a chronic, frequently progressive, failure of lymphatic drainage. This disorder is frequently genetic in origin, and a multigenerational family in which eight individuals developed postnatal lymphoedema of all four limbs was ascertained from the joint Lymphoedema/Genetic clinic at St George's Hospital. Methods: Linkage analysis was used to determine a locus, and exome sequencing was employed to look for causative variants. Results: Linkage analysis revealed cosegregation of a 16.1 Mb haplotype on chromosome 1q42 that contained 173 known or predicted genes. Whole exome sequencing in a single affected individual was undertaken, and the search for the causative variant was focused to within the linkage interval. This approach revealed two novel non-synonymous single nucleotide substitutions within the chromosome 1 locus, in NVL and GJC2. NVL and GJC2 were sequenced in an additional cohort of individuals with a similar phenotype and non-synonymous variants were found in GJC2 in four additional families. Conclusion: This report demonstrates the power of exome sequencing efficiently applied to a traditional positional cloning pipeline in disease gene discovery, and suggests that the phenotype produced by GJC2 mutations is predominantly one of 4 limb lymphoedema

    Long-Term Declines in Disability Among Older Men: Medical Care, Public Health, and Occupational Change

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    Functional disability (difficulty in walking , difficulty in bending, paralysis, blindness in at least one eye, and deafness in at least one ear) in the United States has fallen at an average annual rate of 0.6 percent among men age 50 to 74 from the early twentieth century to the early 1990s. Twenty-four to 41 percent of this decline is attributable to innovations in medical care, 37 percent to reduced chronic disease rates, and the remainder is unexplained. The portion due to reduced chronic disease rates can be subdivided into the 9 percent accounted for by reduced infectious disease rates (particularly rheumatic fever, malaria, typhoid, and acute respiratory infections), the 7 percent accounted for by occupational shifts away from manual labor and to white collar jobs, and the 21 percent that is unexplained.
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