We studied 19 symptomatic female carriers of the Duchenne muscular dystrophy (DMD) gene. Most of these dystrophinopathy patients had had an erroneous or ambiguous diagnosis prior to dystrophin immunofluorescence testing. We assessed clinical severity by a standardized protocol, measured X-chromosome inactivation patterns in blood and muscle DNA, and quantitated the dystrophin protein content of muscle. We found that patients could be separated into two groups: those showing equal numbers of normal and mutant dystrophin genes in peripheral blood DNA ("random" X-inactivation), and those showing preferential use of the mutant dystrophin gene ("skewed" X-inactivation). In the random X-inactivation carriers, the clinical phenotype ranged from asymptomatic to mild disability, the dystrophin content of muscle was > 60% of normal, and there were only minor histopathologic changes. In the skewed X-inactivation patients, clinical manifestations ranged from mild to severe, but the patients with mild disease were young (5 to 10 years old). The low levels of dystrophin (< 30% on average) and the severe symptoms of the older patients suggested a poor prognosis for those with skewed X-inactivation, and they all showed morphologic changes of dystrophy. The random inactivation patients showed evidence of biochemical "normalization," with higher dystrophin content in muscle than predicted by the number of normal dystrophin genes. Seventy-nine percent of skewed X-inactivation patients (11/14) showed genetic "normalization," with proportionally more dystrophin-positive nuclei in muscle than in blood. In 65% of the skewed X-inactivation patients, dystrophin was not produced by dystrophin-positive nuclei; an average of 20% of myofiber nuclei were genetically dystrophin-positive but did not produce stable dystrophin. Biochemical normalization seems to be the main mechanism for rescue of fibers from dystrophin deficiency in the random X-inactivation patients. In the skewed X-inactivation patients, genetic normalization is active, but production failure of dystrophin by dystrophin-normal nuclei may counteract any effect of biochemical normalization. In the skewed X-inactivation patients, the remodeling of the muscle through cycles of degeneration and regeneration led to threefold increase in the number of dystrophin-competent nuclei in muscle myofibers (3.3 +/- 4.6), while dystrophin content was on the average 1.5-fold less then expected (-1.54 +/- 3.38). Our results permit more accurate prognistic assessment of isolated female dystrophinopathy patients and provide important data with which to estimate the potential effect of gene delivery (gene therapy) in DMD.
2003: Impacts of tourism development on water demand and beach degradation on the island of Mallorca (Spain). Geogr. Ann., 85 A (3-4): 287-300.ABSTRACT. The development of tourism in Mallorca has led to the island's economy being based, almost exclusively, on this sector. Since 1955 mass tourism has affected the economic and social structures of Mallorca. The development was based on a rapid growth of tourist demand and on a chaotic development of tourist facilities. This has had severe consequences for the island: insufficiently controlled urban planning, overcrowded beaches, and erosion of the beach-dune system caused by massive construction on the coastal zone. Many beaches have been transformed into urban beaches and their coastline has retreated. Solutions like sand renourishment have not stopped the erosion process. The increasing number of residents and visitors exerts a strong pressure over water resources producing overextraction and a lowering of the groundwater table in aquifers. A strong seasonal concentration of visitors in coastal summer resorts represents a high peak demand during the dry season. The exhaustion of groundwater resources and the higher water demand are managed with environmentally and economically expensive resources such as seawater desalination. The results show that the dwelling capacity of the island has been exceeded and the present levels of water demand and beach degradation are not sustainable. This indicates that tourism in Mallorca is becoming unsustainable and a water and coastal management policy is urgently required if sustainability is to be achieved.
This paper presents empirical research analyzing the politeness strategies used by male and female Venezuelan Spanish Speakers in two role-play situations: inviting and responding to an invitation. When inviting, participants preferred using solidarity over deference politeness strategies, and strategies that would threaten their own and their interlocutor's freedom of action. There were differences between male and female participation. Females were more verbose than males and, in the first two stages of the interaction -making the invitation and responding to the refusal -more deferential. They only showed solidarity when parting. Males, on the other hand, were deferential only when making the invitation, but showed solidarity -read 'became aggressive' -upon receiving the refusal and when parting. Unlike what happened when inviting, when responding to the invitation participants were highly deferential. This time, however, males were more deferential than females. These instead struck more balance between being deferential and friendly. Once more, participants preferred strategies that would curtail their own and their interlocutor's freedom of action, rather than those that would express disapproval of themselves and/or the interlocutor. The results from this research show that Venezuelans -at least those that participated in this study -belong to a positive politeness culture where the preferred rules of rapport are: 1. Be friendly; and 2. Impose, in that order.
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